Diversity, equity, and inclusion in clinical trials: A practical guide from the perspective of a trial sponsor.

Background: Considering diversity, equity, and inclusion (DEI) in clinical trials ensures that data collected for investigational treatments reflect the populations most likely to benefit from those therapies. Resources and recommendations regarding DEI were assembled by the trial sponsor to assist clinical trial development.

Methods: A cross-disciplinary team from the sponsoring organization was assembled to inform trial planning and collate resources that promote DEI throughout the clinical trial life cycle.

Emraclidine, a novel positive allosteric modulator of cholinergic M4 receptors, for the treatment of schizophrenia: a two-part, randomised, double-blind, placebo-controlled, phase 1b trial.

Background: Emraclidine is a novel, brain-penetrant, highly selective M4 receptor positive allosteric modulator in development for the treatment of schizophrenia. We aimed to evaluate the safety and tolerability of multiple ascending doses of emraclidine in patients with schizophrenia.

Methods: We conducted a two-part, randomised, phase 1b trial in the USA.

Case Distribution, Sources, and Breeds of Dogs Presenting to a Veterinary Behavior Clinic in the United States from 1997 to 2017.

The purpose of this retrospective case study was to evaluate trends over time in case distribution, sources, and breeds of dogs presenting to the behavioral medicine service at a veterinary college referral hospital in the United States. For case distribution and sources, the available records from the behavior service (n = 1923) from 1997 to 2017 were evaluated. Breeds of dogs presenting to all services (n = 51,052) were compared to behavior cases (n = 822) from 2007 to 2016.

A cross-species approach to disorders affecting brain and behaviour.

Structural and functional elements of biological systems are highly conserved across vertebrates. Many neurological and psychiatric conditions affect both humans and animals. A cross-species approach to the study of brain and behaviour can advance our understanding of human disorders via the identification of unrecognized natural models of spontaneous disorders, thus revealing novel factors that increase vulnerability or resilience, and via the assessment of potential therapies.

The safety and tolerability of aripiprazole once-monthly as maintenance treatment for bipolar I disorder: A double-blind, placebo-controlled, randomized withdrawal study.

Background: Aripiprazole once-monthly 400 mg (AOM 400), an atypical long-acting injectable antipsychotic, has demonstrated efficacy and safety in maintenance treatment of bipolar I disorder (BP-I). We further assess safety and tolerability and characterize adverse events (AEs) across the duration of aripiprazole exposure.

Methods: Patients with BP-I were stabilized on oral aripiprazole (2-8 weeks), AOM 400 (12-28 weeks), followed by 1:1 randomization of patients meeting stability criteria to a 52-week, double-blind, placebo-controlled withdrawal phase.

Symptoms and functioning with aripiprazole once-monthly injection as maintenance treatment for bipolar I disorder.

Background: Effects of maintenance treatment with aripiprazole once-monthly 400mg (AOM 400) on symptoms and functioning were assessed in adults with bipolar I disorder (BP-I) after a manic episode.

Methods: Patients were stabilized on oral aripiprazole, cross-titrated to AOM 400, then randomized in a 52-week, double-blind, placebo-controlled, withdrawal phase. Prespecified secondary outcomes are reported: time to hospitalization for mood episode, Young Mania Rating Scale (YMRS), Montgomery-Åsberg Depression Rating Scale (MADRS), Clinical Global Impression-Bipolar scale, Functioning Assessment Short Test (FAST), and Brief Quality of Life in Bipolar Disorder questionnaire.

Aripiprazole Once-Monthly in the Treatment of Acute Psychotic Episodes in Schizophrenia: Post Hoc Analysis of Positive and Negative Syndrome Scale Marder Factor Scores.

Background: Long-acting injectable antipsychotics are treatment options for acute and long-term treatment of patients with schizophrenia. In a previously published 12-week randomized, double-blind, placebo-controlled clinical trial of patients with schizophrenia experiencing an acute psychotic episode, aripiprazole once-monthly 400 mg (AOM 400) produced significantly greater improvement than placebo on the primary endpoint, Positive and Negative Syndrome Scale (PANSS) total score at week 10.

Methods: To examine the efficacy of AOM 400 across a broader representation of schizophrenia symptoms, including agitation, a post hoc analysis of this trial was carried out to assess the change in PANSS Marder factor domains (positive symptoms, negative symptoms, disorganized thought, uncontrolled hostility/excitement, and anxiety/depression) and the PANSS excited component (equivalent to Marder factor domain uncontrolled hostility/excitement plus the tension item) by comparing differences in change from baseline between AOM 400 and placebo using a mixed model for repeated measures.

Efficacy and Safety of Aripiprazole Once-Monthly in the Maintenance Treatment of Bipolar I Disorder: A Double-Blind, Placebo-Controlled, 52-Week Randomized Withdrawal Study.

Objective: To evaluate efficacy, safety, and tolerability of long-acting injectable antipsychotic aripiprazole once-monthly 400 mg (AOM 400) as maintenance treatment for bipolar I disorder (BP-I).

Methods: In a double-blind, placebo-controlled, 52-week randomized withdrawal study conducted from August 2012 to April 2016, patients with a DSM-IV-TR diagnosis of BP-I currently experiencing a manic episode were stabilized sequentially on oral aripiprazole and AOM 400 and then randomized to AOM 400 or placebo. The primary end point was time from randomization to recurrence of any mood episode.

Switching from Inadequate Adjunctive or Combination Treatment Options to Brexpiprazole Adjunctive to Antidepressant: An Open-Label Study on the Effects on Depressive Symptoms and Cognitive and Physical Functioning.

Background: Approximately 50% of patients with major depressive disorder do not respond adequately to their antidepressant treatment, underscoring the need for more effective treatment options. The objective of this study was to investigate the effect of adjunctive brexpiprazole on depressive symptoms in patients with major depressive disorder who were not responding to adjunctive or combination therapy of their current antidepressant treatments with several different classes of agents (NCT02012218).

Methods: In this 6-week, open-label, phase 3b study, patients with major depressive disorder who had an inadequate response to ≥1 adjunctive or combination therapy, in addition to history of ≥1 failure to monotherapy antidepressant treatment, were switched to adjunctive brexpiprazole.

Adjunctive brexpiprazole in patients with major depressive disorder and anxiety symptoms: an exploratory study.

Background: Major depressive disorder (MDD) with concurrent anxiety symptoms may signal a difficult-to-treat patient. Brexpiprazole is a serotonin-dopamine activity modulator: a partial agonist at 5-HT and dopamine D receptors at similar potency, and an antagonist at 5-HT and noradrenaline alpha receptors. The objective of this Phase IIIb study was to explore effectiveness, safety, and tolerability of brexpiprazole adjunctive to antidepressant (ADT) monotherapy in patients with MDD and anxiety symptoms (NCT02013531).

The effect of brexpiprazole in adult outpatients with early-episode schizophrenia: an exploratory study.

The aim of this study was to evaluate flexibly dosed brexpiprazole for early-episode schizophrenia through the assessment of efficacy, social functioning, and tolerability. This was an exploratory, 16-week, open-label, flexible-dose (1, 2, 3, or 4 mg/day; target dose 3 mg/day) study in outpatients with early-episode schizophrenia (18-35 years old, ≤5 years' duration of illness). Efficacy was assessed by the Positive and Negative Syndrome Scale score (PANSS) and social functioning was assessed by changes from baseline in PANSS modified prosocial subscale, personal and social performance (PSP), and specific levels of functioning (SLOF) scales.

Effects of aripiprazole once-monthly on symptoms of schizophrenia in patients switched from oral antipsychotics.

Objective: To assess the effects of aripiprazole once-monthly 400 mg (AOM 400) on clinical symptoms and global improvement in schizophrenia after switching from an oral antipsychotic.

Methods: In a multicenter, open-label, mirror-image, naturalistic study in patients with schizophrenia (>1 year, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision [DSM-IV-TR] criteria), changes in efficacy measures were assessed during prospective treatment (6 months) with AOM 400 after switching from standard-of-care oral antipsychotics. During prospective treatment, patients were cross-titrated to oral aripiprazole monotherapy (1-4) weeks followed by open-label AOM 400 (24 weeks).

Brexpiprazole as an adjunctive treatment in young adults with major depressive disorder who are in a school or work environment.

Background: Major depressive disorder (MDD) is a common, debilitating disorder with substantial socioeconomic burden. Many patients with MDD experience symptoms that impair functioning and productivity, often negatively affecting work or educational pursuits. This Phase 3b open-label study evaluated adjunctive brexpiprazole in young adults with MDD, who were in work or study.

The effect of brexpiprazole (OPC-34712) and aripiprazole in adult patients with acute schizophrenia: results from a randomized, exploratory study.

The aim of this study was to explore the effects of brexpiprazole and aripiprazole on efficacy, cognitive functioning, and safety in patients with acute schizophrenia. Patients who would benefit from hospitalization/continued hospitalization for acute relapse of schizophrenia were enrolled and randomized (2 : 1) to target doses of open-label brexpiprazole 3 mg/day or aripiprazole 15 mg/day for 6 weeks. Outcomes included change from baseline to week 6 in the Positive and Negative Syndrome Scale total score, Barratt Impulsiveness Scale 11-item score, and Cogstate computerized cognitive test battery scores.

Patient-Centered Outcomes with Aripiprazole Once-Monthly for Maintenance Treatment in Patients with Schizophrenia: Results From Two Multicenter, Randomized, Double-Blind Studies.

Objectives: To further characterize the clinical profile of long-term treatment with aripiprazole once-monthly 400 mg (AOM 400) by examining patient-centered outcomes in adults with schizophrenia.

Methods: Data are from 2 separate studies: a 52-week, multicenter, randomized, double-blind, placebo-controlled study and a 38-week, multicenter, randomized, double-blind, active-controlled study that evaluated the clinical profile of AOM 400 as maintenance treatment in patients with schizophrenia. The studies were conducted from July 2008 through February 2011 and from September 2008 through August 2012, respectively.

Aripiprazole once-monthly 400 mg for long-term maintenance treatment of schizophrenia: a 52-week open-label study.

Background: Long-term maintenance treatment with an antipsychotic is often required to prevent relapse and mitigate functional deterioration in patients with schizophrenia.

Aims: This study assessed the long-term safety, tolerability, and maintenance of the therapeutic effect of aripiprazole once-monthly 400 mg (AOM 400) in patients with schizophrenia.

Methods: This 52-week, open-label study included patients previously enrolled in 1 of 2 AOM 400 randomized controlled trials (RCTs) and de novo patients.

Effects of aripiprazole once-monthly on domains of personal and social performance: results from 2 multicenter, randomized, double-blind studies.

Objective: To assess the effects of maintenance therapy with aripiprazole once-monthly 400mg on personal and social functioning.

Methods: Data were analyzed from 2 randomized, double-blind trials of patients with schizophrenia requiring chronic antipsychotic treatment. One study was a 52-week trial of aripiprazole once-monthly 400mg versus placebo; the other was a 38-week trial of aripiprazole once-monthly 400mg, oral aripiprazole (10-30 mg daily), and aripiprazole once-monthly 50mg (subtherapeutic dose to test assay sensitivity).

Aripiprazole once-monthly in the acute treatment of schizophrenia: findings from a 12-week, randomized, double-blind, placebo-controlled study.

Objective: To evaluate aripiprazole once-monthly (AOM), a long-acting injectable suspension of aripiprazole, as acute treatment in patients with schizophrenia (DSM-IV-TR).

Method: Adults experiencing an acute psychotic episode were randomized to 12 weeks of double-blind treatment with AOM 400 mg or placebo (October 2012-August 2013). The primary efficacy outcome was change from baseline to endpoint (week 10) in Positive and Negative Syndrome Scale (PANSS) total score.

Aripiprazole once-monthly for treatment of schizophrenia: double-blind, randomised, non-inferiority study.

Background: Long-acting injectable formulations of antipsychotics are treatment alternatives to oral agents.

Aims: To assess the efficacy of aripiprazole once-monthly compared with oral aripiprazole for maintenance treatment of schizophrenia.

Method: A 38-week, double-blind, active-controlled, non-inferiority study; randomisation (2:2:1) to aripiprazole once-monthly 400 mg, oral aripiprazole (10-30 mg/day) or aripiprazole once-monthly 50 mg (a dose below the therapeutic threshold for assay sensitivity).

The relation of maternal fluid balance to offspring passive immunity.

The objectives were to measure changes in fluid balance of mares at parturition and relate those changes to the foals' acquisition of passive immunity. Twelve Thoroughbred mares and their foals were observed for suckling behavior for the first 12h post-partum. The mare's water intake, packed cell volume, plasma protein concentration, and plasma osmolality were measured pre- and post-partum.

Aripiprazole intramuscular depot as maintenance treatment in patients with schizophrenia: a 52-week, multicenter, randomized, double-blind, placebo-controlled study.

Objective: To evaluate the efficacy and tolerability of a once-monthly intramuscular (IM) depot formulation of the dopamine partial agonist aripiprazole as maintenance treatment in adults meeting DSM-IV-TR schizophrenia criteria.

Method: The study was conducted from July 2008 until February 2011. Subjects requiring chronic treatment with an antipsychotic entered a 4- to 12-week oral stabilization phase and received oral aripiprazole (10-30 mg/d).

Hyperalgesia in outpatients with dermal injury: quantitative sensory testing versus a novel simple technique.

Objective: Dermal inflammation from many causes may produce a reversible period of hyperalgesia (increased sensitivity to pain perception) or allodynia (pain from innocuous stimuli). Hyperalgesia and allodynia have received relatively little attention in clinical trials of acute pain. We sought to quantitate tactile allodynia and thermal hyperalgesia in outpatients presenting with acute dermal injuries.