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Fu D.-J.,Janssen Scientific Affairs LLC | Turkoz I.,Janssen Research and Development LLC | Bruce Simonson R.,Clinical Development | Walling D.P.,Janssen Research and Development LLC | And 4 more authors.
Journal of Clinical Psychiatry | Year: 2015

Objective: Schizoaffective disorder is a complex illness for which optimal treatment is not well established. Results of the first controlled, relapse-prevention study of paliperidone palmitate once-monthly injectable (paliperidone monthly) in schizoaffective disorder are presented. Method: The study was conducted between September 20, 2010, and October 22, 2013. Patients with schizoaffective disorder (confirmed by the Structured Clinical Interview for DSM-IV Axis I Disorders) experiencing acute exacerbation of psychotic and depressive/manic symptoms were stabilized with paliperidone monthly as monotherapy or as adjunctive therapy to mood stabilizers or antidepressants and randomly assigned (1:1) to paliperidone monthly or placebo in a 15-month, double-blind, relapse-prevention phase. Randomization was stratified by administration as monotherapy or adjunctive therapy and by study center. The primary endpoint was time to relapse. Results: 334 patients were evaluated. Paliperidone monthly significantly delayed time to relapse for psychotic, depressive, and manic symptoms compared with placebo (P < .001, log-rank test). Relapse risk was 2.49 times greater for placebo (hazard ratio = 2.49; 95% CI, 1.55 to 3.99; P < .001, Cox proportional hazards model). Overall relapse rates were 33.5% for placebo and 15.2% for paliperidone monthly. For monotherapy, relapse risk was 3.38 times greater with placebo (P = .002), and for adjunctive treatment it was 2.03 times greater with placebo (P = .021). Paliperidone monthly was superior to placebo in maintaining functioning as measured by the Personal and Social Performance scale (P = .014, mixed-model repeated-measures analysis). The most common adverse events (placebo, paliperidone monthly) were increased weight (4.7%, 8.5%), insomnia (7.1%, 4.9%), schizoaffective disorder (5.9%, 3.0%), headache (3.5%, 5.5%), and nasopharyngitis (3.5%, 5.5%). Incidence of any extrapyramidal-related adverse event was 7.1% for placebo and 8.5% for paliperidone monthly. Conclusions: Paliperidone monthly as monotherapy or adjunctive therapy significantly delayed psychotic, depressive, and/or manic relapses; reduced their risk; and better maintained functioning in patients with schizoaffective disorder. Results support the value of maintenance treatment with paliperidone monthly in schizoaffective disorder. © Copyright 2015 Physicians Postgraduate Press, Inc. Source

Nowak R.M.,Ford Motor Company | Parker J.M.,Clinical Development | Silverman R.A.,North Shore Long Island Jewish Medical Center | Rowe B.H.,University of Alberta | And 5 more authors.
American Journal of Emergency Medicine | Year: 2015

Background Patients with frequent asthma exacerbations resulting in emergency department (ED) visits are at increased risk for future exacerbations. We examined the ability of 1 dose of benralizumab, an investigational antiinterleukin 5 receptor α monoclonal antibody, to reduce recurrence after acute asthma exacerbations.Methods In this randomized, double-blind, placebo-controlled study, eligible subjects presented to the ED with an asthma exacerbation, had partial response to treatment, and greater than or equal to 1 additional exacerbation within the previous year. Subjects received 1 intravenous infusion of placebo (n = 38) or benralizumab (0.3 mg/kg, n = 36 or 1.0 mg/kg, n = 36) added to outpatient management. The primary outcome was the proportion of subjects with greater than or equal to 1 exacerbation at 12 weeks in placebo vs the combined benralizumab groups. Other outcomes included the time-weighted rate of exacerbations at week 12, adverse events, blood eosinophil counts, asthma symptom changes, and health care resource utilization.Results The proportion of subjects with greater than or equal to 1 asthma exacerbation at 12 weeks was not different between placebo and the combined benralizumab groups (38.9% vs 33.3%; P =.67). However, compared with placebo, benralizumab reduced asthma exacerbation rates by 49% (3.59 vs 1.82; P =.01) and exacerbations resulting in hospitalization by 60% (1.62 vs 0.65; P =.02) in the combined groups. Benralizumab reduced blood eosinophil counts but did not affect other outcomes, while demonstrating an acceptable safety profile.Conclusions When added to usual care, 1 dose of benralizumab reduced the rate and severity of exacerbations experienced over 12 weeks by subjects who presented to the ED with acute asthma. © 2014 Elsevier Inc. Source

Decramer M.,Catholic University of Leuven | Anzueto A.,University of Texas Health Science Center at San Antonio | Kerwin E.,Southern Research Institute | Kaelin T.,Lowcountry Lung and Critical Care | And 5 more authors.
The Lancet Respiratory Medicine | Year: 2014

Background: Combination long-acting bronchodilator treatment might be more effective than long-acting bronchodilator monotherapy for the treatment of chronic obstructive pulmonary disease (COPD). We aimed to compare the efficacy and safety of umeclidinium (UMEC) plus vilanterol (VI) with tiotropium (TIO) monotherapy, UMEC monotherapy, or VI monotherapy in patients with moderate to very severe COPD. Methods: In two multicentre, randomised, blinded, double-dummy, parallel-group, active-controlled trials, eligible patients (current or former smokers aged 40 years or older with an established clinical history of COPD) were randomly assigned in 1:1:1:1 ratio to UMEC 125 μg plus VI 25 μg, UMEC 62·5 μg plus VI 25 μg, TIO 18 μg, and either VI 25 μg (study 1) or UMEC 125 μg (study 2). All study drugs were used once daily for 24 weeks. TIO was delivered via the HandiHaler inhaler and all other active treatments were delivered via the ELLIPTA dry powder inhaler. Random assignment (by a validated computer-based system) was done by centre and was not stratified. All patients and physicians were masked to assigned treatment during the studies. The primary efficacy endpoint of both studies was trough forced expiratory volume in 1 s (FEV1) on day 169, which was analysed in the intention-to-treat population. Both studies are registered with ClinicalTrials.gov, numbers NCT01316900 (study 1) and NCT01316913 (study 2). Findings: 1141 participants were recruited in study 1, and 1191 in study 2. For study 1, after exclusions, 208, 209, 214, and 212 patients were included in the intention-to-treat analyses for TIO monotherapy, VI monotherapy, UMEC 125 μg plus VI 25 μg, and UMEC 62·5 μg plus VI 25 μg, respectively. For study 2, 215, 222, 215, and 217 patients were included in the intention-to-treat analyses for TIO monotherapy, UMEC monotherapy, UMEC 125 μg plus VI 25 μg, and UMEC 62·5 μg plus VI 25 μg, respectively. In both studies, we noted improvements in trough FEV1 on day 169 for both doses of UMEC plus VI compared with TIO monotherapy (study 1, UMEC 125 μg plus VI 25 μg: 0·088 L [95% CI 0·036 to 0·140; p=0·0010]; study 1, UMEC 62·5 μg plus VI 25 μg: 0·090 L [0·039 to 0·141; p=0·0006]; study 2, UMEC 125 μg plus VI 25 μg: 0·074 L [0·025 to 0·123; p=0·0031]; study 2, UMEC 62·5 μg plus VI 25 μg: 0·060 L [0·010 to 0·109; nominal p=0·0182]). Both doses of UMEC plus VI also improved trough FEV1 compared with VI monotherapy (UMEC 125 μg plus VI 25 μg: 0·088 L [0·036 to 0·140; p=0·0010]; UMEC 62·5 μg plus VI 25 μg: 0·090 L [0·039 to 0·142; p=0·0006], but not compared with UMEC 125 μg monotherapy (UMEC 125 μg plus VI 25 μg: 0·037 L [-0·012 to 0·087; p=0·14]; UMEC 62·5 μg plus VI 25 μg: 0·022 L [-0·027 to 0·072; p=0·38]). All treatments produced improvements in dyspnoea and health-related quality of life; we noted no significant differences in symptoms, health status, or risk of exacerbation between UMEC plus VI and TIO. The most common on-treatment, severe-intensity adverse event in both studies was acute exacerbation of COPD (1-4 [<1-2%] patients across treatment groups in study 1 and 1-6 [<1-3%] patients in study 2). We recorded five to 15 (2-7%) on-treatment serious adverse events across treatment groups in study 1, and nine to 22 (4-10%) in study 2. We noted no substantial changes from baseline in vital signs, clinical laboratory findings, or electrocardiography findings in any of the treatment groups. Interpretation: Combination treatment with once-daily UMEC plus VI improved lung function compared with VI monotherapy and TIO monotherapy in patients with COPD. Overall our results suggest that the combination of UMEC plus VI could be beneficial for the treatment of moderate to very severe COPD. Funding: GlaxoSmithKline. © 2014 Elsevier Ltd. Source

Tran T.N.,Astrazeneca | Khatry D.B.,Translational Sciences, Inc. | Ke X.,Astrazeneca | Ward C.K.,Translational Sciences, Inc. | Gossage D.,Clinical Development
Annals of Allergy, Asthma and Immunology | Year: 2014

Background The clinical importance of eosinophils in asthma has been shown by the observation of frequent exacerbation in patients with high sputum eosinophil counts and a corresponding decrease in exacerbations when anti-inflammatory therapy was adjusted to maintain low sputum eosinophil percentages. However, less is known of the relation between blood eosinophilia and asthma exacerbation. Objective To examine whether patients with asthma and a higher blood eosinophil count have more asthma attacks than those with a lower count. Methods The authors analyzed data from the National Health and Nutrition Examination Survey, an annual cross-sectional survey of the US general population. Patients with asthma and asthma attacks were identified based on participants' self-report or parental report. A high blood eosinophil count was defined using 200, 300, or 400 cells/μL as cutoffs. The primary analysis used data from 2001 through 2010 after adjusting for demographic variables, obesity, smoking, neutrophil level, and past treatment for wheezing. A secondary analysis used data from 2007 through 2010 and included recent treatment for asthma and fraction of exhaled nitric oxide level as additional adjustment variables. Results In survey years 2001 through 2010, 3,162 patients with asthma had blood eosinophil data and approximately half (54% of children and 52% of adults) reported an asthma attack in the previous year. In the primary analysis, higher blood eosinophil counts were associated with more asthma attacks in children but not in adults. The secondary analysis suggested an association in both children and adults. Conclusion Patients with asthma with higher blood eosinophil counts experienced more asthma attacks than those with lower eosinophil counts. © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. Source

Despite substantial morbidity associated with respiratory syncytial virus (RSV) infection, there is no licensed vaccine. MEDI-559 is a live attenuated intranasal vaccine candidate being developed for prevention of lower respiratory illness due to RSV in young children. This randomized, placebo-controlled study evaluated safety of MEDI-559 in healthy, RSV-seronegative children. MEDI-559 or placebo was administered on 3 occasions, 2 months apart. Primary safety was based on solicited symptoms (SSs) and adverse events (AEs) collected for 28 days after each dose. Nasal wash samples were collected 3 times after each dose (days 7-10, 12-18, 28-34) and at sick visits. Serum was collected for measuring antibody immune responses to RSV prior to first vaccination and 28 days post final dose. Long-term safety was monitored for 365 days from first dose. SSs were mild and frequent (MEDI-559 84%; placebo 91%); most common SSs were runny/stuffy nose, cough, and irritability/fussiness. AEs occurred in 67% MEDI-559 and 57% placebo recipients: most common AE was upper respiratory tract infection (MEDI-559 35%; placebo 23%). Higher incidence of medically attended lower respiratory illness within 28 days after dosing occurred in the MEDI-559 arm compared to placebo (none associated with vaccine virus shedding). There was no evidence of enhanced RSV disease. Vaccine virus was detected only in MEDI-559 recipients; shedding occurred in 56%subjects, primarily post dose 1. A functional immune response was observed in 59% and 9% MEDI-559 and placebo recipients, respectively, by an RSV microneutralization assay. Vaccine take, assessed by proportion that shed vaccine-type virus or had a seroresponse against RSV, was seen in 95% MEDI-559 subjects. MEDI-559 is therefore biologically active and immunogenic in this seronegative pediatric population. Although the frequency of SSs and AEs was not considered clinically significant, the increase in medically attended lower respiratory illnesses in the vaccine group warrants expanded safety studies. ClinicalTrials.gov NCT00767416. Source

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