Efficacy and safety of vixotrigine in idiopathic or diabetes-associated painful small fibre neuropathy (CONVEY): a phase 2 placebo-controlled enriched-enrolment randomised withdrawal study.

Background: No pharmacological treatments are specifically indicated for painful small fibre neuropathy (SFN). CONVEY, a phase 2 enriched-enrolment study, evaluated the efficacy and safety of vixotrigine, a voltage- and use-dependent sodium channel blocker, in participants with idiopathic or diabetes-associated painful SFN.

Methods: CONVEY was a phase 2, multicentre, placebo-controlled, double-blind (DB), enriched-enrolment, randomised withdrawal study.

Evaluation of the Effect of Uridine Diphosphate-Glucuronosyltransferases (UGT) Inhibition by Valproic Acid on Vixotrigine Pharmacokinetics in Healthy Volunteers.

Background And Objective: Vixotrigine is a voltage-dependent and use-dependent sodium channel blocker in development for the treatment of neuropathic pain. Metabolism of vixotrigine is primarily through glucuronidation, resulting in the major M13 metabolite. Two additional major metabolites formed are M14 and M16.

Design of Phase 3 Studies Evaluating Vixotrigine for Treatment of Trigeminal Neuralgia.

Purpose: Vixotrigine (BIIB074) is a voltage- and use-dependent sodium channel blocker. These studies will evaluate the efficacy and safety of vixotrigine in treating pain experienced by patients with trigeminal neuralgia (TN) using enriched enrollment randomized withdrawal trial designs.

Patients And Methods: Two double-blind randomized withdrawal studies are planned to evaluate the efficacy and safety of vixotrigine compared with placebo in participants with TN (NCT03070132 and NCT03637387).

A phase III randomized controlled trial of tiotropium add-on therapy in children with severe symptomatic asthma.

Background: Studies in adults and adolescents have demonstrated that tiotropium is efficacious as an add-on therapy to inhaled corticosteroids (ICSs) with or without other maintenance therapies in patients with moderate or severe symptomatic asthma.

Objective: We sought to assess the efficacy and safety of once-daily tiotropium Respimat add-on therapy to high-dose ICS with 1 or more controller medications, or medium-dose ICS with 2 or more controller medications, in the first phase III trial of tiotropium in children with severe symptomatic asthma.

Methods: In this 12-week, double-blind, placebo-controlled, parallel-group trial, 401 participants aged 6 to 11 years were randomized to receive once-daily tiotropium 5 μg (2 puffs of 2.

Daily home-based spirometry during withdrawal of inhaled corticosteroid in severe to very severe chronic obstructive pulmonary disease.

The WISDOM study (NCT00975195) reported a change in lung function following withdrawal of fluticasone propionate in patients with severe to very severe COPD treated with tiotropium and salmeterol. However, little is known about the validity of home-based spirometry measurements of lung function in COPD. Therefore, as part of this study, following suitable training, patients recorded daily home-based spirometry measurements in addition to undergoing periodic in-clinic spirometric testing throughout the study duration.

Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease after withdrawal of inhaled corticosteroids: a post-hoc analysis of the WISDOM trial.

Background: Blood eosinophil counts might predict response to inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD) and a history of exacerbations. We used data from the WISDOM trial to assess whether patients with COPD with higher blood eosinophil counts would be more likely to have exacerbations if ICS treatment was withdrawn.

Methods: WISDOM was a 12-month, randomised, parallel-group trial in which patients received 18 μg tiotropium, 100 μg salmeterol, and 1000 μg fluticasone propionate daily for 6 weeks and were then randomly assigned (1:1) electronically to receive either continued or reduced ICS over 12 weeks.

Efficacy of BI 671800, an oral CRTH2 antagonist, in poorly controlled asthma as sole controller and in the presence of inhaled corticosteroid treatment.

The prostaglandin D2 (PGD2) receptor, CRTH2, plays a role in allergic airway inflammation. The efficacy of BI 671800, a CRTH2 antagonist, was assessed in 2 separate trials in patients with asthma, in either the absence or the presence of inhaled corticosteroid (ICS) therapy. In this study, BI 671800 (50, 200 or 400 mg) and fluticasone propionate (220 μg) all given twice daily (bid) were compared with bid placebo in symptomatic controller-naïve adults with asthma (Trial 1), and BI 671800 400 mg bid compared with montelukast 10 mg once daily (qd), and matching placebo bid, in patients with asthma receiving inhaled fluticasone (88 μg bid) (Trial 2).

A randomised, open-label phase II trial of afatinib versus cetuximab in patients with metastatic colorectal cancer.

Purpose: This randomised phase II trial aimed to compare efficacy of the irreversible ErbB family blocker, afatinib, with cetuximab in patients with KRAS wild-type metastatic colorectal adenocarcinoma (mCRC) with progression following oxaliplatin- and irinotecan-based regimens. Efficacy in patients with KRAS mutations was also evaluated.

Patients And Methods: Patients with KRAS wild-type tumours were randomised 2:1 to afatinib (40 mg/day, increasing to 50 mg/day if minimal toxicity) or cetuximab weekly (400 mg/m2 loading dose, then 250 mg/m2/week) according to number of previous chemotherapy lines.

Withdrawal of inhaled glucocorticoids and exacerbations of COPD.

Background: Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long-acting bronchodilators has not been fully explored.

Methods: In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid fluticasone propionate (500 μg twice daily) during a 6-week run-in period.

Stepwise withdrawal of inhaled corticosteroids in COPD patients receiving dual bronchodilation: WISDOM study design and rationale.

Long-acting bronchodilators in combination with inhaled corticosteroids (ICS) are recommended to decrease the risk of recurrent exacerbations in patients with Global initiative for chronic Obstructive Lung Disease (GOLD) stage 3-4 chronic obstructive pulmonary disease (COPD). There is increasing concern about the clinical benefit and long-term safety of ICS use in COPD patients. The WISDOM (Withdrawal of Inhaled Steroids During Optimised bronchodilator Management) study (NCT00975195) aims to evaluate the need for ICS use via stepwise withdrawal of ICS in COPD patients (GOLD 3-4 with a history of at least one exacerbation during the 12-month period prior to screening) receiving dual bronchodilation.