scholarly journals 0535 Evaluation of Insomnia Symptoms in a Double-Blind, Randomized, Placebo-Controlled Phase 3 Trial of Sage-217 in Postpartum Depression

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A204-A205
Author(s):  
A Mittal ◽  
K Deligiannidis ◽  
M Huang ◽  
E Suthoff ◽  
S Acaster ◽  
...  
Keyword(s):  
Postpartum Depression ◽  
Primary Endpoint ◽  
Repeated Measures ◽  
Rating Scale ◽  
Depression Symptoms ◽  
Upper Respiratory Tract ◽  
Major Depressive ◽  
Phase 3 ◽  
Post Hoc ◽  
Insomnia Symptoms

Abstract Introduction Postpartum depression (PPD) is a specifier of major depressive disorder (MDD) with peripartum onset. SAGE-217, an investigational, oral neuroactive steroid GABAA receptor positive allosteric modulator, demonstrated improvements in depressive and anxiety symptoms versus placebo in a Phase 3 trial in PPD (NCT02978326; ROBIN) and a pivotal trial in MDD (NCT03000530). In PPD and MDD, insomnia symptoms are key diagnostic features, comorbid sleep disorders are frequent, and insomnia is a common residual symptom. Here we conducted post-hoc analyses to assess insomnia symptoms in the ROBIN trial. Methods Women (n=151) ages 18-45, ≤6 months postpartum, with PPD (major depressive episode beginning in 3rd trimester or ≤4 weeks postpartum) and a Hamilton Rating Scale for Depression (HAM-D) total score ≥26, were randomized 1:1 to receive outpatient SAGE-217 30mg or placebo for two weeks, with 4 weeks follow-up. Change from baseline (CFB) in HAM-D score at Day 15 was the primary endpoint. Secondary endpoints included CFB in HAM-D at other time points and the Montgomery-Åsberg Depression Rating Scale (MADRS). Post-hoc analyses assessed HAM-D insomnia subscale (HAM-D-Ins) and MADRS individual insomnia item (MADRS-Ins) scores. HAM-D and MADRS measures were evaluated using a mixed-effects model for repeated measures. Safety and tolerability were assessed by adverse event (AE) reporting. Results SAGE-217 demonstrated statistically significant Day 15 CFB versus placebo in HAM-D (primary endpoint: -17.8 vs. -13.6, p=0.0028), MADRS (-22.1 vs. -17.6, p=0.0180), and associated insomnia sub-scales/items (difference SAGE-217 vs. placebo; HAM-D-Ins: -1.003, p=0.0038; MADRS-Ins: -0.773, p=0.0116). Significant CFB in insomnia sub-scales/items favoring SAGE-217 were observed by Day 3 (HAM-D-Ins: -0.841, p=0.0142; MADRS-Ins: -0.710, p=0.017) and at Day 45 (HAM-D-Ins: -0.730, p=0.0207; MADRS-Ins: -0.636, p=0.0221). Most common (≥5%) AEs were somnolence, headache, dizziness, upper respiratory tract infection, diarrhea, and sedation. Conclusion SAGE-217 demonstrated improvements in depression symptoms, including insomnia symptoms, and was generally well tolerated. Support This study was sponsored by Sage Therapeutics, Inc.

scholarly journals Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study

2017 ◽  
Author(s):  
Olivier Lortholary ◽  
Marie Olivia Chandesris ◽  
Cristina Bulai Livideanu ◽  
Carle Paul ◽  
Gérard Guillet ◽  
...  
Keyword(s):  
Placebo Group ◽  
Adverse Events ◽  
Primary Endpoint ◽  
Repeated Measures ◽  
Rating Scale ◽  
Systemic Mastocytosis ◽  
Estimating Equation ◽  
Phase 3 ◽  
Cumulative Response ◽  
Indolent Systemic Mastocytosis

Background:Indolent systemic mastocytosis, including the subvariant of smouldering systemic mastocytosis, is a lifelong condition associated with reduced quality of life. Masitinib inhibits KIT and LYN kinases that are involved in indolent systemic mastocytosis pathogenesis. We aimed to assess safety and efficacy of masitinib versus placebo in severely symptomatic patients who were unresponsive to optimal symptomatic treatments.Methods:In this randomised, double-blind, placebo-controlled, phase 3 study, we enrolled adults (aged 18–75 years) with indolent or smouldering systemic mastocytosis, according to WHO classification or documented mastocytosis based on histological criteria, at 50 centres in 15 countries. We excluded patients with cutaneous or non-severe systemic mastocytosis after a protocol amendment. Patients were centrally randomised (1:1) to receive either oral masitinib (6 mg/kg per day over 24 weeks with possible extension) or matched placebo with minimisation according to severe symptoms. The primary endpoint was cumulative response (≥75% improvement from baseline within weeks 8–24) in at least one severe baseline symptom from the following: pruritus score of 9 or more, eight or more flushes per week, Hamilton Rating Scale for Depression of 19 or more, or Fatigue Impact Scale of 75 or more. We assessed treatment effect using repeated measures methodology for rare diseases via the generalised estimating equation model in a modified intention-to-treat population, including all participants assigned to treatment minus those who withdrew due to a non-treatment-related cause. We assessed safety in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00814073. Findings: Between Feb 19, 2009, and July 15, 2015, 135 patients were randomly assigned to masitinib (n=71) or placebo (n=64). By 24 weeks, masitinib was associated with a cumulative response of 18·7% in the primary endpoint (122·6 responses of 656·5 possible responses [weighted generalised estimating equation]) compared with 7·4% for placebo (48·9 of 656·5; difference 11·3%; odds ratio 3·6; 95% CI 1·2–10·8; p=0·0076). Frequent severe adverse events (>4% difference from placebo) were diarrhoea (eight [11%] of 70 in the masitinib group vs one [2%] of 63 in the placebo group), rash (four [6%] vs none), and asthenia (four [6%] vs one [2%]). The most frequent serious adverse events were diarrhoea (three patients [4%] vs one [2%]) and urticaria (two [3%] vs none), and no life-threatening toxicities occurred. One patient in the placebo group died (unrelated to study treatment). Interpretation:These study findings indicate that masitinib is an effective and well tolerated agent for the treatment of severely symptomatic indolent or smouldering systemic mastocytosis. Funding: AB Science (Paris, France)

scholarly journals The efficacy of levomilnacipran ER across symptoms of major depressive disorder: a post hoc analysis of 5 randomized, double-blind, placebo-controlled trials

CNS Spectrums ◽  
2016 ◽  
Vol 21 (5) ◽  
pp. 385-392 ◽  
Author(s):  
Roger S. McIntyre ◽  
Carl Gommoll ◽  
Changzheng Chen ◽  
Adam Ruth
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Rating Scale ◽  
Phase Iii ◽  
Depression Symptoms ◽  
Major Depressive ◽  
Double Blind ◽  
Post Hoc Analysis ◽  
Symptom Domains ◽  
Post Hoc

ObjectiveA post hoc analysis evaluated the effects of levomilnacipran ER on individual symptoms and symptom domains in adults with major depressive disorder (MDD).MethodsData were pooled from 5 Phase III trials comprising 2598 patients. Effects on depression symptoms were analyzed based on change from baseline in individual Montgomery–Åsberg Depression Rating Scale (MADRS) item scores. A1dditional evaluations included resolution of individual symptoms (defined as a MADRS item score ≤1 at end of treatment) and concurrent resolution of all 10 MADRS items, all MADRS6 subscale items, and all items included in different symptom clusters (Dysphoria, Retardation, Vegetative Symptoms, Anhedonia).ResultsSignificantly greater mean improvements were found on all MADRS items except Reduced Appetite with levomilnacipran ER treatment compared with placebo. Resolution of individual symptoms occurred more frequently with levomilnacipran ER than placebo for each MADRS item (all P<.05), with odds ratios (ORs) ranging from 1.26 to 1.75; resolution of all 10 items was also greater with levomilnacipran ER (OR=1.57; P=.0051). Significant results were found for the MADRS6 subscale (OR=1.73; P<.0001) and each symptom cluster (OR range, 1.39 [Vegetative Symptoms] to 1.84 [Retardation]; all clusters, P<.01).ConclusionAdult MDD patients treated with levomilnacipran ER improved across a range of depression symptoms and symptom domains.

scholarly journals Lurasidone for major depressive disorder with mixed features and irritability: a post-hoc analysis

CNS Spectrums ◽  
2017 ◽  
Vol 22 (2) ◽  
pp. 228-235 ◽  
Author(s):  
Alan C. Swann ◽  
Maurizio Fava ◽  
Joyce Tsai ◽  
Yongcai Mao ◽  
Andrei Pikalov ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Repeated Measures ◽  
Mixed Model ◽  
Rating Scale ◽  
Major Depressive ◽  
Double Blind ◽  
Post Hoc Analysis ◽  
Mixed Features ◽  
Post Hoc

ObjectiveThe aim of this post-hoc analysis was to evaluate the efficacy of lurasidone in treating major depressive disorder (MDD) with mixed features including irritability.MethodsThe data in this analysis were derived from a study of patients meeting DSM–IV–TR criteria for unipolar MDD, with a Montgomery–Åsberg Depression Rating Scale (MADRS) total score ≥26, presenting with two or three protocol-defined manic symptoms, and who were randomized to 6 weeks of double-blind treatment with either lurasidone 20–60 mg/d (n=109) or placebo (n=100). We defined “irritability” as a score ≥2 on both the Young Mania Rating Scale (YMRS) irritability item (#5) and the disruptive-aggressive item (#9). Endpoint change in the MADRS and YMRS items 5 and 9 were analyzed using a mixed model for repeated measures for patients with and without irritability.ResultsSome 20.7% of patients met the criteria for irritability. Treatment with lurasidone was associated with a significant week 6 change vs. placebo in MADRS score in both patients with (–22.6 vs. –9.5,p<0.0001, effect size [ES]=1.4) and without (–19.9 vs. –13.8,p<0.0001,ES=0.7) irritability. In patients with irritable features, treatment with lurasidone was associated with significant week 6 changes vs. placebo in both the YMRS irritability item (–1.4 vs. –0.3,p=0.0012,ES=1.0) and the YMRS disruptive-aggressive item (–1.0 vs. –0.3,p=0.0002,ES=1.2).ConclusionsIn our post-hoc analysis of a randomized, placebo-controlled, 6-week trial, treatment with lurasidone significantly improved depressive symptoms in MDD patients with mixed features including irritability. In addition, irritability symptoms significantly improved in patients treated with lurasidone.

The Role of Conductor Facial Expression in Students’ Evaluation of Ensemble Expressivity

2012 ◽  
Vol 60 (4) ◽  
pp. 419-429 ◽  
Author(s):  
Brian A. Silvey
Keyword(s):  
Facial Expression ◽  
Facial Expressions ◽  
Wind Ensemble ◽  
Repeated Measures ◽  
Rating Scale ◽  
High School Band ◽  
Band Students ◽  
Point Rating Scale ◽  
Post Hoc

The purpose of this study was to explore whether conductor facial expression affected the expressivity ratings assigned to music excerpts by high school band students. Three actors were videotaped while portraying approving, neutral, and disapproving facial expressions. Each video was duplicated twice and then synchronized with one of three professional wind ensemble recordings. Participants ( N = 133) viewed nine 1-min videos of varying facial expressions, actors, and excerpts and rated each ensemble’s expressivity on a 10-point rating scale. Results of a one-way repeated measures ANOVA indicated that conductor facial expression significantly affected ratings of ensemble expressivity ( p < .001, partial η2 = .15). Post hoc comparisons revealed that participants’ ensemble expressivity ratings were significantly higher for excerpts featuring approving facial expressions than for either neutral or disapproving expressions. Participants’ mean ratings were lowest for neutral facial expression excerpts, indicating that an absence of facial affect influenced evaluations of ensemble expressivity most negatively.

scholarly journals A randomized, double-blind, placebo-controlled 6-wk trial of the efficacy and tolerability of 5 mg vortioxetine in adults with major depressive disorder*

2012 ◽  
Vol 16 (2) ◽  
pp. 313-321 ◽  
Author(s):  
Rakesh Jain ◽  
Atul R. Mahableshwarkar ◽  
Paula L. Jacobsen ◽  
Yinzhong Chen ◽  
Michael E. Thase
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Rating Scale ◽  
P Value ◽  
Depression Symptoms ◽  
Major Depressive ◽  
Double Blind ◽  
Efficacy Measure ◽  
Efficacy Measures ◽  
Hamilton Anxiety Scale

Abstract Vortioxetine (Lu AA21004) is a multi-modal antidepressant in clinical development for the treatment of major depressive disorder (MDD). The current study evaluated the efficacy and tolerability of 5 mg vortioxetine compared to placebo after 6 wk of treatment in adults with MDD in an out-patient setting. Adults aged 18–75 yr, with a diagnosis of MDD and a baseline Montgomery–Asberg Depression Rating Scale (MADRS) total score ⩾30, were randomized to receive either 5 mg vortioxetine or placebo over 6 wk, followed by a 2-wk medication-free discontinuation period. The primary efficacy measure was change from baseline in Hamilton Rating Scale for Depression (HAMD)-24 total score at week 6 compared to placebo. Additional measures included response and remission rates, Clinical Global Impression Scale – Improvement scores, HAMD-24 total score in subjects with baseline Hamilton Anxiety Scale (HAMA) >19 and MADRS-S total score. Adverse events (AEs) were assessed throughout the study. A total of 600 adults were randomized. There were no significant differences in efficacy measures between subjects in the 5 mg vortioxetine and placebo groups at week 6. HAMD-24 total score in subjects with baseline HAMA >19 in the 5 mg vortioxetine group was improved at weeks 3–6 compared to the placebo group (nominal p value <0.05). The most common AEs for the vortioxetine and placebo groups were nausea (19.1 and 9.4%), headache (17.1 and 15.1%) and diarrhoea (11.4 and 7.0%), respectively. In this study of adults with MDD, 5 mg vortioxetine did not differ significantly from placebo in reducing depression symptoms after 6 wk of treatment.

Evaluation of Insomnia Symptoms in a Double-Blind, Randomized, Placebo-Controlled Phase 3 Trial of Zuranolone in Postpartum Depression

2021 ◽  
Vol 89 (9) ◽  
pp. S91
Author(s):  
Kristina Deligiannidis ◽  
Ming-Yi Huang ◽  
Ellison Suthoff ◽  
Sarah Acaster ◽  
Moshe Fridman ◽  
...  
Keyword(s):  
Postpartum Depression ◽  
Phase 3 ◽  
Double Blind ◽  
Insomnia Symptoms

scholarly journals Lurasidone for major depressive disorder with mixed features and anxiety: a post-hoc analysis of a randomized, placebo-controlled study

CNS Spectrums ◽  
2017 ◽  
Vol 22 (2) ◽  
pp. 236-245 ◽  
Author(s):  
Joyce Tsai ◽  
Michael E. Thase ◽  
Yongcai Mao ◽  
Daisy Ng-Mak ◽  
Andrei Pikalov ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Rating Scale ◽  
Controlled Study ◽  
Madrs Total Score ◽  
Major Depressive ◽  
Post Hoc Analysis ◽  
Mixed Features ◽  
Post Hoc ◽  
Severe Anxiety

ObjectiveThe aim of this post-hoc analysis was to evaluate the efficacy of lurasidone in treating patients with major depressive disorder (MDD) with mixed features who present with mild and moderate-to-severe levels of anxiety.MethodsThe data in this analysis were derived from a study of patients meeting the DSM–IV–TR criteria for unipolar MDD, with a Montgomery–Åsberg Depression Rating Scale (MADRS) total score ≥26, presenting with two or three protocol-defined manic symptoms, who were randomized to 6 weeks of double-blind treatment with either lurasidone 20–60 mg/day (n=109) or placebo (n=100). Anxiety severity was evaluated using the Hamilton Anxiety Rating Scale (HAM–A). To evaluate the effect of baseline anxiety on response to lurasidone, the following two anxiety groups were defined: mild anxiety (HAM–A≤14) and moderate-to-severe anxiety (HAM–A≥15). Change from baseline in MADRS total score was analyzed for each group using a mixed model for repeated measures.ResultsTreatment with lurasidone was associated with a significant week 6 change versus placebo in MADRS total score for patients with both mild anxiety (–18.4 vs. –12.8, p<0.01, effect size [ES]=0.59) and moderate-to-severe anxiety (–22.0 vs. –13.0, p<0.001, ES=0.95). Treatment with lurasidone was associated with a significant week 6 change versus placebo in HAM–A total score for patients with both mild anxiety (–7.6 vs. –4.0, p<0.01, ES=0.62), and moderate-to-severe anxiety (–11.4 vs. –6.1, p<0.0001, ES=0.91).ConclusionsIn this post-hoc analysis of an MDD with mixed features and anxiety population, treatment with lurasidone was associated with significant improvement in both depressive and anxiety symptoms in subgroups with mild and moderate-to-severe levels of anxiety at baseline.

scholarly journals Effects of Cariprazine on Cognition in Patients With Bipolar Mania or Mixed States: Post Hoc Analysis From 3 Randomized, Controlled Phase III Studies

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 182-182
Author(s):  
Roger S. Mcintyre ◽  
Eduard Vieta ◽  
Willie Earley ◽  
Mehul Patel
Keyword(s):  
Repeated Measures ◽  
Missing Values ◽  
Rating Scale ◽  
Phase Iii ◽  
Cognitive Symptoms ◽  
Double Blind ◽  
Bipolar I Disorder ◽  
Post Hoc Analysis ◽  
Cognitive Subscale ◽  
Post Hoc

AbstractIntroductionCariprazine, a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist, is approved for the treatment of schizophrenia and for depressive, manic, or mixed episodes associated with bipolar I disorder. Previous post hoc analyses have demonstrated that cariprazine was effective versus placebo for improving cognitive symptoms in patients with schizophrenia or bipolar depression. This post hoc analysis evaluated the effects of cariprazine on cognitive symptoms in patients with acute manic or mixed bipolar episodes.MethodsData from 3 phase II/III, randomized, double-blind, placebo-controlled studies in patients with manic or mixed episodes associated with bipolar I disorder (NCT00488618, NCT01058096, NCT01058668) were pooled and analyzed. Patients were randomized to placebo or flexibly dosed cariprazine (3-12 mg/d, 3-6 mg/d, or 6-12 mg/d [1 study only]) for 3 weeks of double-blind treatment; all dose groups were combined for the pooled analysis. Cognitive symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) Cognitive subscale (sum of PANSS items P2, N5, N7, G10, G11); a score of 15 or greater at baseline indicated the presence of cognitive symptoms. Mean changes from baseline to week 3 in PANSS cognitive subscale/item scores and Young Mania Rating Scale (YMRS) total score were evaluated in the overall intent-to-treat (ITT) population and in the subgroup of patients with baseline cognitive symptoms. A mixed-effects model for repeated measures (MMRM) was used to impute missing values.ResultsOf the 1012 patients in the ITT population, 174 (placebo=71; cariprazine=103) had a PANSS Cognitive subscale score of 15 or greater at baseline. At week 3, the cariprazine group demonstrated significantly greater mean improvement than the placebo group on PANSS cognitive subscale scores in both the ITT population (−2.2 vs −1.3; P<.0001) and the subgroup with baseline cognitive symptoms (−4.0 vs −1.9; P=.0002). In patients with baseline cognitive symptoms, improvement was significantly greater for cariprazine- versus placebo-treated patients on YMRS total score (−16.7 vs −8.2; P<.0001) and the individual PANSS cognitive subscale items of conceptual disorganization (−1.1 vs −0.5; P=.0004), difficulty in abstract thinking (−0.8 vs −0.3; P=.0044), stereotyped thinking (−0.3 vs −0.1; P=.0350), and poor attention (−1.1 vs −0.6; P=.0043).ConclusionIn patients with manic or mixed episodes associated with bipolar I disorder, cariprazine versus placebo was effective in improving cognitive symptoms in the overall patient population as well as in patients with baseline cognitive symptoms. In addition, cariprazine versus placebo also demonstrated efficacy in improving manic symptoms in patients with baseline cognitive symptoms. These results suggest that cariprazine may provide benefits for the treatment of cognitive symptoms in patients with bipolar I mania.FundingAbbVie Inc.

scholarly journals The Effects of Erratic Ratings on Placebo Response and Signal Detection in the Roche Bitopertin Phase 3 Negative Symptom Studies—A Post Hoc Analysis

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Daniel Umbricht ◽  
Alan Kott ◽  
David G Daniel
Keyword(s):  
Negative Symptom ◽  
Repeated Measures ◽  
Drug Response ◽  
Negative Symptoms ◽  
Placebo Response ◽  
Phase 3 ◽  
Post Hoc Analysis ◽  
Mixed Response ◽  
Post Hoc ◽  
The Impact

Abstract Objective In the current post hoc analyses, we assessed the impact of erratic ratings, a marker of questionable measurement quality, on placebo and drug response and drug-placebo separation in schizophrenia negative symptom trials. Methods Data were obtained from three phase 3, multi-center, 24-week, randomized, double-blind, placebo-controlled trials with bitopertin in the treatment of negative symptoms of schizophrenia. Erratic ratings were operationally defined as at least one occurrence of at least a 20% change in negative symptom factor score in the opposite direction at consecutive visits. The effect of erratic ratings on placebo and drug response and drug-placebo separation was assessed by the protocol on a subject and site-level using a mixed model repeated measures analysis. Results Placebo response was significantly increased in the presence of erratic ratings, both at the subject and site levels. Treatment response in the presence of erratic ratings was mixed and inconsistent across doses and protocols. In most cases removing data generated by subjects and sites with erratic ratings resulted in a numerical increase of drug-placebo difference favoring treatment. Additionally, in this post hoc analysis, 10 mg of bitopertin separated statistically significantly from placebo at the end of study in one of the protocols. Discussion Erratic rating patterns appear to be consistently associated with increased response to placebo and a mixed response to treatment in the bitopertin negative symptoms trials and to have degraded drug-placebo separation. As a quality indicator, they may flag the need for enhanced quality control of affected sites in clinical trials.

scholarly journals Predicting response to treatment and discriminating bipolar and depression symptoms using Hamilton Depression Rating Scale

2017 ◽  
Vol 66 (3) ◽  
pp. 125-130 ◽  
Author(s):  
Adriana Munhoz Carneiro ◽  
André Cavalcanti ◽  
Lucas de Francisco Carvalho ◽  
Ricardo Alberto Moreno
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Rating Scale ◽  
Response To Treatment ◽  
Depression Symptoms ◽  
Type I ◽  
Major Depressive ◽  
Bipolar Type ◽  
The Difference ◽  
Almost All

ABSTRACT Objective The present study aims to compare the diagnostic ability of the HAMD 17 items with shorter versions of 7 and 6 items. Methods A total of 133 patients from a 6 month clinical trial diagnosed with mood disorders (60.2% with Major Depressive Disorder and 39.8% with bipolar type I disorder) were recruited. Results The 17 items HAMD scale showed similar results as compared with shorter versions. Furthermore, almost all patients’ diagnosed with Major Depressive Disorder scored more compared to Bipolar Disorder, but the difference was not significant. Conclusion This study allows that the use of a shorter version of HAMD might be an adequate possibility, and also that depressive symptoms were similar among groups.

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