scholarly journals Efficacy of galcanezumab in patients with migraine who did not benefit from commonly prescribed preventive treatments

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dulanji K. Kuruppu ◽  
Joshua Tobin ◽  
Yan Dong ◽  
Sheena K. Aurora ◽  
Laura Yunes-Medina ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Migraine Headache ◽  
Mixed Model ◽  
Preventive Treatment ◽  
Response Rates ◽  
Toxin A ◽  
Double Blind ◽  
Preventive Medication ◽  
Onabotulinum Toxin A ◽  
Post Hoc

Abstract Background Galcanezumab is a calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) indicated for the preventive treatment of migraine. While galcanezumab has demonstrated efficacy in patients who did not respond to prior preventive medications in general, its efficacy in patients who did not benefit from individual, commonly prescribed preventive treatments due to inadequate efficacy or safety/tolerability remains unknown. Methods CONQUER was a 3-month, randomized, double-blind, placebo-controlled, phase 3b study that enrolled patients with episodic or chronic migraine who had 2 to 4 migraine preventive medication category failures in the past 10 years. Patients were randomly assigned 1:1 to receive placebo (N = 230) or galcanezumab 120 mg/month (240 mg loading dose; N = 232). Post hoc analyses were conducted to determine the efficacy of galcanezumab in patients who had not benefited from six of the most commonly prescribed migraine preventive medications. The mean change from baseline in monthly migraine headache days and ≥ 50 % response rates were assessed over months 1–3. Improvement in Migraine-Specific Questionnaire Role Function-Restrictive (MSQ-RFR) scores were assessed at month 3. The endpoints were estimated via mixed model with repeated measures. Results The most common treatment failures due to inadequate efficacy or safety/tolerability, which at least 20 % of patients reported trying without benefit, included topiramate, amitriptyline, propranolol, valproate or divalproex, onabotulinum toxin A, and metoprolol. Patients who had not previously benefited from these treatments had a greater mean reduction in monthly migraine headache days across months 1–3 in the galcanezumab group compared to placebo (all p < 0.01). More patients treated with galcanezumab experienced a ≥ 50 % reduction from baseline in monthly migraine headache days across months 1–3 compared to placebo (all p < 0.05). Galcanezumab-treated patients had a greater improvement in mean MSQ-RFR scores at month 3 compared to placebo (all p < 0.01). Conclusions In this population, galcanezumab was effective in reducing monthly migraine headache days, improving response rates, and enhancing quality of life in patients who had not previously benefited from topiramate, amitriptyline, propranolol, valproate or divalproex, onabotulinum toxin A, and/or metoprolol due to inadequate efficacy or safety/tolerability. Trial registration ClinicalTrials.gov NCT03559257 (CONQUER).

scholarly journals Early onset of effect following galcanezumab treatment in patients with previous preventive medication failures

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Todd J. Schwedt ◽  
Dulanji K. Kuruppu ◽  
Yan Dong ◽  
Katherine Standley ◽  
Laura Yunes-Medina ◽  
...  
Keyword(s):  
Early Onset ◽  
Migraine Headache ◽  
Preventive Treatment ◽  
Double Blind ◽  
The Past ◽  
Link Type ◽  
Calcitonin Gene ◽  
Preventive Medication ◽  
Statistical Separation ◽  
Post Hoc

Abstract Background Galcanezumab is a monoclonal antibody (mAb) that binds calcitonin gene-related peptide (CGRP) and is indicated for the preventive treatment of migraine. Galcanezumab demonstrated early onset of effect in patients with migraine but it is unknown whether the same holds true for patients who have not benefited from multiple prior migraine preventives. Methods Patients with episodic or chronic migraine from a 3-month, randomized, double-blind, placebo-controlled, phase 3b study (CONQUER) who had 2 to 4 migraine preventive medication category failures in the past 10 years were randomized 1:1 to placebo (N = 230) or galcanezumab 120 mg/month (240 mg loading dose; N = 232). In this post-hoc analysis, change from baseline in number of monthly and weekly migraine headache days was assessed. Monthly onset of effect was the earliest month at which significant improvement with galcanezumab compared to placebo was achieved and maintained at all subsequent months. Weekly onset was the initial week at which statistical separation was achieved and maintained at all subsequent weeks during that month. Proportion of patients with migraine headache days in the first week of treatment, and patients achieving ≥50%, ≥75%, and 100% response by month and week were also assessed. Results Galcanezumab-treated patients had a significantly greater reduction in monthly migraine headache days starting at month 1, which remained significant for all subsequent months compared to placebo (all p ≤ 0.0001, month 1 mean change from baseline: placebo − 0.7; galcanezumab − 4.0). Weekly migraine headache days was significantly reduced in galcanezumab-treated patients starting at week 1 and continued for each subsequent week of month 1 compared to placebo (all p < 0.01, week 1 mean change from baseline: placebo − 0.2; galcanezumab − 1.1). A significantly smaller percentage of patients had a migraine headache on the first day after galcanezumab treatment compared to placebo (28.4% vs 39.2%) and at each subsequent day during week 1 (all p < 0.05). A greater proportion of galcanezumab-treated patients achieved ≥50%, ≥75%, and 100% response at months 1–3 (all p < 0.05) and at weeks 1–4 of month 1 compared to placebo (all p < 0.01). Conclusion Galcanezumab showed early onset of effect beginning the day after treatment initiation in patients who had not previously benefited from migraine preventive treatments. Trial registration ClinicalTrials.gov, NCT03559257. Registered 18 June 2018.

Medication overuse in a subgroup analysis of phase 3 placebo-controlled studies of galcanezumab in the prevention of episodic and chronic migraine

Cephalalgia ◽  
2020 ◽  
pp. 033310242096665
Author(s):  
David W Dodick ◽  
Erin G Doty ◽  
Sheena K Aurora ◽  
Dustin D Ruff ◽  
Virginia L Stauffer ◽  
...  
Keyword(s):  
Chronic Migraine ◽  
Subgroup Analysis ◽  
Repeated Measures ◽  
Migraine Headache ◽  
Medication Overuse ◽  
Preventive Treatment ◽  
Episodic Migraine ◽  
Phase 3 ◽  
Double Blind ◽  
Acute Medication

Introduction Acute medication overuse is prevalent in patients with migraine. Methods In three phase 3, double-blind, randomized, placebo-controlled studies, patients with episodic migraine (EVOLVE-1 and EVOLVE-2) or chronic migraine (REGAIN) were randomized 2:1:1 to monthly subcutaneous injections of placebo or galcanezumab 120 or 240 mg for 3 or 6 months. This subgroup analysis evaluated mean changes in the number of monthly migraine headache days in each treatment among patients with versus without baseline acute medication overuse via mixing modelling with repeated measures. Results The percentages of patients with baseline medication overuse in placebo, galcanezumab 120-mg and 240-mg groups, respectively, were 19.4%, 17.3%, and 19.3% for EVOLVE-1/-2 (pooled; post hoc), and 63.4%, 64.3%, and 64.1% for REGAIN ( a priori). Both galcanezumab doses demonstrated significant improvement compared with placebo for overall least squares mean change in monthly migraine headache days in patients with baseline medication overuse in both the episodic and chronic migraine studies ( p ≤ 0.001). Furthermore, both galcanezumab doses reduced average monthly medication overuse rates compared to placebo ( p < 0.001) in both patient populations with medication overuse at baseline. Conclusions Galcanezumab appears to be effective for the preventive treatment of episodic and chronic migraine in patients who overuse acute medications. Trial registration: ClinicalTrials.gov Identifiers: NCT02614183, NCT02614196, and NCT02614261

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 Efficacy of Lurasidone on PANSS Subscales in Adolescent Patients with Schizophrenia: Results from a 6-week, Double-blind, Placebo-controlled, Multicenter Study

2017 ◽  
Vol 41 (S1) ◽  
pp. S90-S91 ◽  
Author(s):  
C. Correll ◽  
R. Goldman ◽  
J. Cucchiaro ◽  
L. Deng ◽  
A. Loebel
Keyword(s):  
Repeated Measures ◽  
Mixed Model ◽  
Wide Spectrum ◽  
Dose Range ◽  
Data Safety Monitoring Board ◽  
Double Blind ◽  
Meaningful Improvement ◽  
General Psychopathology ◽  
Adolescent Patients ◽  
Adjusted Least Squares

IntroductionLurasidone is an atypical antipsychotic that demonstrated efficacy in the treatment of adults with schizophrenia in the dose range of 37–148 mg/day.Objective/AimsThe objective of this analysis was to evaluate the efficacy of lurasidone in adolescent patients with schizophrenia.MethodsAdolescents (13–17 years old) diagnosed with schizophrenia were randomly assigned to six weeks of double-blind treatment with lurasidone 37 mg/day, 74 mg/day or placebo. Changes from baseline to week 6 in PANSS total and subscale (positive, negative, general psychopathology, excitability) scores were evaluated using mixed-model repeated-measures analysis.ResultsA total of 326 patients (mean age, 15.4 years) were randomized and received lurasidone 37 mg/day (n = 108), 74 mg/day (n = 106), or placebo (n = 112). The PANSS total score at week 6 demonstrated a placebo-adjusted, least-squares (LS) mean improvement of –8.0 (P < 0.001; effect size [ES], 0.51) for the 37 mg/day group and –7.7 (P < 0.001; ES = 0.48) for the 74 mg/day group. Placebo-adjusted LS mean change for lurasidone 37 mg/day and 74 mg/day, respectively, was –3.2 (P < 0.001; ES = 0.62) and –3.2 (P < 0.001; ES = 0.60) on the PANSS positive subscale, –1.7 (P = 0.011; ES = 0.41) and –1.6 (P = 0.022; ES = 0.35) on the PANSS negative subscale, –2.8 (P = 0.012; ES = 0.38) and –2.8 (P = 0.011; ES = 0.37) on the PANSS general psychopathology subscale, and –1.1 (P = 0.016; ES = 0.36) and –1.8 (P < 0.001; ES = 0.53) on the PANSS excitability subscale.ConclusionsIn adolescent patients with schizophrenia, lurasidone (37 mg/day and 74 mg/day) demonstrated statistically significant efficacy and clinically meaningful improvement across a wide spectrum of symptoms associated with schizophrenia. Sponsored by Sunovion Pharmaceuticals Inc. ClinicalTrials.gov identifier: NCT01911429.Disclosure of interestDr Correll reports being a consultant and/or advisor for Alkermes, Forum Pharmaceuticals Inc., Gerson Lehrman Group, IntraCellular Therapies, Janssen/J&J, Lundbeck, Medavante, Medscape, Otsuka, Pfizer Inc, ProPhase, Sunovion Pharmaceuticals Inc., Supernus, Takeda, and Teva providing expert testimony for Bristol-Myers Squibb Company, Janssen, and Otsuka serving on a Data Safety Monitoring Board for Lundbeck and Pfizer Inc and receiving grant support from Takeda. Drs Goldman, Cucchiaro, Deng and Loebel are employees of Sunovion Pharmaceuticals Inc.

Post hoc analysis of a randomised, placebo-controlled, active-reference 6-week study of brexpiprazole in acute schizophrenia

2020 ◽  
Vol 32 (3) ◽  
pp. 153-158 ◽  
Author(s):  
Stephen R. Marder ◽  
Hans Eriksson ◽  
Yudong Zhao ◽  
Mary Hobart
Keyword(s):  
Adverse Events ◽  
Repeated Measures ◽  
Mixed Model ◽  
Least Square ◽  
Analysis Of Covariance ◽  
Sensitivity Analyses ◽  
Symptom Improvement ◽  
Syndrome Scale ◽  
Quetiapine Xr ◽  
Post Hoc

AbstractObjective:We provide a closer look at the result of a randomised, placebo-controlled, active-reference (quetiapine XR), flexible-dose, 6-week study of brexpiprazole in schizophrenia, which did not meet its primary endpoint – change from baseline in Positive and Negative Syndrome Scale (PANSS) total score. We also investigate potential expectancy bias from the well-known side-effect profile of the active reference that could have affected the study outcome.Methods:Pre-specified sensitivity analyses of the primary end point were performed using analysis of covariance (ANCOVA) last observation carried forward (LOCF) and observed cases (OC). Post hoc analyses of change from baseline in PANSS total score were performed using the mixed model for repeated measures approach with treatment groups split by having typical adverse events with potential for functional unblinding, for example, somnolence, increase in weight, dizziness, dry mouth and sedation.Results:Pre-specified sensitivity analyses showed separation from placebo for brexpiprazole at week 6: LOCF, ANCOVA: −4.3 [95% CI (−8.0, −0.5), p = 0.0254]. OC, ANCOVA: −3.9 [95% CI (−7.3, −0.5), p = 0.0260]. Patients treated with brexpiprazole experiencing typical adverse events with potential for functional unblinding before or at Week 2 had a least square (LS) mean PANSS change of −29.5 (improvement), with a difference in change from baseline to Week 6 in PANSS total score between brexpiprazole and placebo of −13.5 [95% CI (−23.1, −4.0), p = 0.0057], and those who did not had an LS mean change of −18.9 and a difference between brexpiprazole and placebo of −2.9 [95% CI (−7.2, 1.4), p = 0.1809].Conclusion:Pre-specified sensitivity analyses showed separation from placebo for brexpiprazole at Week 6. A post hoc analysis suggested a potential confounding of efficacy rating towards symptom improvement in patients who experience known side effects of quetiapine XR.

Onabotulinum Toxin-A Injections for Nocturnal Bruxism: A Parallel, Double Blind, Placebo Controlled Polysomnographic Study (P05.006)

Neurology ◽  
2012 ◽  
Vol 78 (Meeting Abstracts 1) ◽  
pp. P05.006-P05.006 ◽  
Author(s):  
W. Ondo ◽  
V. Hashem ◽  
C. Hunter ◽  
J. Simmons
Keyword(s):  
Toxin A ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Onabotulinum Toxin A

Efficacy of lurasidone across five symptom dimensions of schizophrenia: Pooled analysis of short-term, placebo-controlled studies

2015 ◽  
Vol 30 (1) ◽  
pp. 26-31 ◽  
Author(s):  
A. Loebel ◽  
J. Cucchiaro ◽  
R. Silva ◽  
Y. Mao ◽  
J. Xu ◽  
...  
Keyword(s):  
Effect Size ◽  
Repeated Measures ◽  
Negative Symptoms ◽  
Mixed Model ◽  
Five Factor Model ◽  
Pooled Analysis ◽  
Positive Symptoms ◽  
Factor Scores ◽  
Short Term ◽  
Double Blind

AbstractObjective:To evaluate the efficacy of lurasidone for schizophrenia using an established five-factor model of the Positive and Negative Syndrome Scale (PANSS).Methods:Patient-level data were pooled from five randomized, double-blind, placebo-controlled, 6-week studies of lurasidone (fixed doses, 40–160 mg/d) for patients with an acute exacerbation of schizophrenia. Changes in five established PANSS factors were assessed using mixed-model repeated measures analysis.Results:Compared with placebo (n = 496), lurasidone (n = 1029, dose groups pooled) significantly improved the PANSS total score at Week 6 (−22.6 vs. −12.8; P < 0.001; effect size, 0.45), as well as all factor scores (P < 0.001 for each): positive symptoms (−8.4 vs. −6.0; effect size, 0.43), negative symptoms (−5.2 vs. −3.3; effect size, 0.33), disorganized thought (−4.9 vs. −2.8; effect size, 0.42), hostility/excitement (−2.7 vs. −1.6; effect size, 0.31), and depression/anxiety (−3.2 vs. −2.3; effect size, 0.31). Separation from placebo occurred at Week 1 for the positive symptoms, disorganized thought, and hostility/excitement factors and at Week 2 for the other factors.Conclusions:In this pooled analysis of short-term studies in patients with acute schizophrenia, lurasidone demonstrated significant improvement for each of the five PANSS factor scores, indicating effectiveness across the spectrum of schizophrenia symptoms.

scholarly journals Triamcinolone Acetonide in the Treatment of Perennial Allergic Rhinitis: A post hoc Efficacy Analysis of a Phase III Study Performed in Russia

2021 ◽  
pp. 1-8
Author(s):  
Alexander V. Karaulov ◽  
Natalia I. Ilina ◽  
Natalia Shartanova ◽  
Aleksandr Maslakov ◽  
Luiz Lucio
Keyword(s):  
Allergic Rhinitis ◽  
Triamcinolone Acetonide ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Nasal Symptom ◽  
Phase Iii ◽  
Double Blind ◽  
Post Hoc Analysis ◽  
Post Hoc ◽  
To Receive

<b><i>Introduction:</i></b> Allergic rhinitis (AR) is a disease which affects &#x3e;24% of the population in Russia. Triamcinolone acetonide (TAA) is a corticosteroid used for treating AR. This post hoc analysis assesses the efficacy of intranasal TAA in improving perennial AR (PAR) symptom scores over 4 weeks. <b><i>Methods:</i></b> NASANIF (NCT03317015) was a double-blind, parallel-group, multicenter, prospective, non-inferiority, phase III clinical trial in which patients with PAR were randomized (1:1) to receive TAA or fluticasone propionate (FP) over 4 weeks. Our post hoc analysis evaluates weekly change in PAR symptoms using the reflective Total Nasal Symptom Score (rTNSS), overall and for individual symptoms (sneezing, nasal itching, rhinorrhoea, and nasal obstruction). Proportion of patients and time to achieve a ≥50 or ≥75% reduction in rTNSS were assessed. For rTNSS endpoints, a linear mixed-model methodology was used; for time-to-event endpoints, cumulative incidence functions were estimated using the Kaplan-Meier method, in the per-protocol population. <b><i>Results:</i></b> Of 260 patients, 128 each completed the study and were randomized to receive TAA or FP. From baseline to week 4, the changes in total rTNSS were −7.78 (95% CI: −8.1701 to −7.3967; <i>p</i> &#x3c; 0.001) and −7.52 (−7.9053 to −7.1320; <i>p</i> &#x3c; 0.001) for TAA and FP, respectively. Individual symptoms improved significantly from baseline. The proportion of patients achieving ≥50 and ≥75% reductions in total rTNSS was 88.0 and 67.2%, respectively in the TAA group. No significant differences were observed between the TAA and FP in any analyses. <b><i>Conclusions:</i></b> TAA produced effective and prolonged improvement of PAR symptoms over a 4-week treatment period.

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