Population pharmacokinetics of eptinezumab in paediatric patients with migraine and dose selection for phase 3 paediatric migraine studies.

This population pharmacokinetics (PopPK) analysis of eptinezumab used data from a paediatric study and a prior adult PopPK model to compare eptinezumab pharmacokinetics between adult and paediatric populations to determine dose recommendations for the phase 3 paediatric studies in migraine. The data consisted of 16 adolescents and 12 children with migraine, with corresponding demographics and 278 plasma concentrations in total. PopPK analysis was performed through nonlinear mixed effect modelling and with prior knowledge taken from a previous PopPK model in adults.

Optimization of acute medication use following eptinezumab initiation during a migraine attack: post hoc analysis of the RELIEF study.

Background: The benefits of preventive treatment on the effectiveness of migraine management have rarely been examined. This post hoc analysis investigated the impact of eptinezumab on the optimization of acute medication effectiveness using the 4-item Migraine Treatment Optimization Questionnaire (mTOQ-4) to measure acute medication optimization over 4 weeks post-infusion.

Methods: RELIEF was a 12-week, phase 3, multicenter, parallel-group, double-blind, placebo-controlled clinical trial conducted in patients aged 18-75 years with a ≥ 1-year history of migraine and 4-15 migraine days per month in the 3 months prior to screening.

Rapid resolution of migraine symptoms after initiating the preventive treatment eptinezumab during a migraine attack: results from the randomized RELIEF trial.

Background: Eptinezumab is an anti-calcitonin gene-related peptide (CGRP) monoclonal antibody approved for the preventive treatment of migraine. In the phase 3 RELIEF study, eptinezumab resulted in shorter time to headache pain freedom and time to absence of most bothersome symptom (MBS; including nausea, photophobia, or phonophobia) compared with placebo when administered during a migraine attack. The objective of this exploratory analysis was to examine the earliest time points that eptinezumab separated from placebo (P < .

Eptinezumab treatment initiated during a migraine attack is associated with meaningful improvement in patient-reported outcome measures: secondary results from the randomized controlled RELIEF study.

Background: Demonstrating therapeutic value from the patient perspective is important in patient-centered migraine management. The objective of this study was to investigate the impact of eptinezumab, a preventive migraine treatment, on patient-reported headache impact, acute medication optimization, and perception of disease change when initiated during a migraine attack.

Methods: RELIEF was a randomized, double-blind, placebo-controlled trial conducted between 2019 and 2020 in adults with ≥1-year history of migraine and 4-15 migraine days per month in the 3 months prior to screening.

Durability of the Clinical Benefit of Droxidopa for Neurogenic Orthostatic Hypotension During 12 Weeks of Open-Label Treatment.

Introduction: Droxidopa is approved to treat neurogenic orthostatic hypotension (nOH) symptoms in patients with autonomic failure based on short-term clinical trial data. Additional data on the long-term efficacy of droxidopa are needed. We have evaluated the 12-week efficacy and tolerability of droxidopa in patients with nOH in an open-label period of an ongoing phase 4 study .

Effects of Intravenous Eptinezumab vs Placebo on Headache Pain and Most Bothersome Symptom When Initiated During a Migraine Attack: A Randomized Clinical Trial.

Importance: Intravenous eptinezumab, an anti-calcitonin gene-related peptide antibody, is approved for migraine prevention in adults. It has established onset of preventive efficacy on day 1 after infusion.

Objective: To evaluate the efficacy of and adverse events related to eptinezumab when initiated during a migraine attack.

Characterization of the changes in supine blood pressure with long-term use of droxidopa in patients with neurogenic orthostatic hypotension.

Background And Aims: Patients with neurogenic orthostatic hypotension (nOH) due to autonomic dysfunction may also experience supine hypertension (defined as supine systolic blood pressure [SBP] ≥140 mmHg). Because pressor agents used to improve nOH symptoms by increasing standing blood pressure (BP) may exacerbate or cause supine hypertension, changes in supine BP with nOH treatments are of interest.

Methods: This post hoc study examined changes in SBP in patients receiving droxidopa (100-600 mg, three times daily) during a 12-month long-term extension study based on whether patients had supine hypertension (ie, supine SBP ≥140 mmHg) at baseline.

Chronobiologic parameter changes in patients with major depressive disorder and sleep disturbance treated with adjunctive brexpiprazole: An open-label, flexible-dose, exploratory substudy.

Background: Circadian rhythm disturbances have been reported in patients with major depressive disorder (MDD). Among these is an increased phase angle between peak cortisol concentration and dim-light melatonin onset (DLMO). The aim of this study was to evaluate changes in chronobiologic parameters of sleep in patients with MDD receiving adjunctive brexpiprazole.

Vortioxetine for attention deficit hyperactivity disorder in adults: A randomized, double-blind, placebo-controlled, proof-of-concept study.

Background: Stimulants remain the mainstay of treatment for attention-deficit hyperactivity disorder (ADHD) but are often associated with insufficient response or poor tolerability, leading to many patients not wishing to be treated with controlled substances.

Aims: This randomized, placebo-controlled, proof-of-concept study (NCT02327013) evaluated the efficacy of a multimodal antidepressant, vortioxetine, in the treatment of ADHD, using a two-stage sequential parallel comparison design.

Methods: Patients aged 18-55 years with a diagnosis of ADHD (DSM-5) and a total score ⩾24 on the Adult ADHD Investigator Symptom Rating Scale (AISRS) were randomized in study stage I with a 1:1:3 ratio to six weeks of treatment with vortioxetine 10 or 20 mg/day, or placebo ( n = 227).

Effect of Brexpiprazole on Prolactin: An Analysis of Short- and Long-Term Studies in Schizophrenia.

Background: Hyperprolactinemia is an undesirable effect of most antipsychotics because of D2-receptor blockade. We assessed the effect of the D2-receptor partial agonist brexpiprazole on prolactin, based on pooled data from three 6-week, randomized, placebo-controlled studies and two open-label extension studies in patients with schizophrenia.

Methods: In the short-term studies, patients received 0.

A randomised, placebo-controlled 24-week study evaluating adjunctive brexpiprazole in patients with major depressive disorder.

Objective: To evaluate brexpiprazole adjunctive to antidepressant therapies (ADTs) as maintenance treatment in patients with major depressive disorder with inadequate response to ADT, utilising a novel study design.

Methods: The study comprised an 8-week prospective treatment period with open-label ADT with double-blind placebo treatment and a 24-week randomised treatment period. Investigators and patients were blinded to treatment periods, randomisation criteria, and timing of randomisation.

Efficacy of vortioxetine on the physical symptoms of major depressive disorder.

Background: Efficacy has been proven for vortioxetine in short-term and long-term treatment of major depressive disorder (MDD), with broad beneficial effects on emotional, physical and cognitive symptoms. Limited specific data on the effects of vortioxetine on depression-related physical symptoms have been published.

Methods: A meta-analysis was carried out of five short-term multinational, double-blind, placebo-controlled studies.

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study.

Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures.

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study.

Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures.

Safety and Tolerability of Desmoteplase Within 3 to 9 Hours After Symptoms Onset in Japanese Patients With Ischemic Stroke.

Background And Purpose: This study investigated the safety and tolerability of desmoteplase administered within 3 to 9 hours after stroke symptoms onset in Japanese patients with acute ischemic stroke.

Methods: Patients were randomized to treatment with either desmoteplase or placebo in a 2:1 ratio in 2 consecutive cohorts (70 μg/kg and then 90 μg/kg). Included patients had a baseline National Institutes of Health Stroke Scale score of 4 to 24 and occlusion or high-grade stenosis in the middle cerebral artery segment M1 or M2 on magnetic resonance angiography.

Refinement of the magnetic resonance diffusion-perfusion mismatch concept for thrombolytic patient selection: insights from the desmoteplase in acute stroke trials.

Background And Purpose: The DIAS-2 study was the only large, randomized, intravenous, thrombolytic trial that selected patients based on the presence of ischemic penumbra. However, DIAS-2 did not confirm the positive findings of the smaller DEDAS and DIAS trials, which also used penumbral selection. Therefore, a reevaluation of the penumbra selection strategy is warranted.

Vascular occlusion enables selecting acute ischemic stroke patients for treatment with desmoteplase.

Background And Purpose: Desmoteplase is a novel and highly fibrin-specific thrombolytic agent. Evidence of safety and efficacy was obtained in 2 phase II trials (Desmoteplase In Acute Ischemic Stroke [DIAS] and Desmoteplase for Acute Ischemic Stroke [DEDAS]). The DIAS-2 phase III trial did not replicate the positive phase II efficacy findings.