179 Dasotraline in Children With Attention Deficit Hyperactivity Disorder: Results of a Randomized, Double-Blind, Placebo-Controlled Study

AbstractObjectivesOnce-daily dosing with dasotraline, a novel dopamine and norepinephrine reuptake inhibitor, achieves stable plasma concentrations over 24 hours with once-daily dosing. This study evaluated dasotraline in children aged 6–12 years (NCT02428088).MethodsPatients were randomized 1:1:1 to 6 weeks of once-daily, fixed-dose dasotraline 2 or 4 mg/day, or placebo. The primary efficacy endpoint was change from baseline (CFB) at Week 6 in ADHD Rating Scale Version IV – Home Version (ADHD RS-IV HV) total score, using a mixed model for repeated measures (MMRM) in the intent-to-treat (ITT) population. Secondary endpoints included Clinical Global Impression-Severity (CGI-S) score and safety endpoints.ResultsThe mean age of 342 randomized patients was 9.1 [SD: 1.9] years; 66.7% were male. Overall, 79% of patients completed the study. In the ITT population (N=336), ADHD RS-IV HV total score improved significantly with dasotraline 4 mg/day vs placebo(least squares [LS] mean [SE] CFB at Week 6: –17.53 [±1.31] vs –11.36 [±1.29], respectively, p<0.001; effect size [ES]: 0.48). Inattentiveness and hyperactivity/impulsivity subscale scores significantly improved with 4 mg/day vs placebo at Week 6 (p=0.001, p=0.003, respectively). Improvement in CGI-S score was statistically significant with dasotraline 4 mg/day vs placebo(LS mean [SE] CFB at Week 6: –1.39 [±0.12] vs –1.04 [±0.12], respectively, p=0.040; ES: 0.29). No significant improvement was observed on the ADHD RS-IV HV total score and the CGI-S score for dasotraline 2 mg/day vs placebo. The most frequent treatment-emergent AEs (≥5% and higher than placebo) were (2 mg/day; 4 mg/day; placebo): insomnia (15.3%; 21.7%; 4.3%, all terms combined), decreased appetite (12.6%; 21.7%; 5.2%), weight loss (5.4%; 8.7%; 0%), irritability (3.6%; 7.0%; 6.0%), nasopharyngitis (0.9%; 5.2%; 0.9%), and nausea (0%; 5.2%; 2.6%).ConclusionsCompared with placebo, dasotraline 4 mg/day significantly improved ADHD symptoms in children, as assessed by ADHD RS-IV HV total score and inattentiveness and hyperactivity/impulsivity subscale scores. Dasotraline was generally well tolerated; most common AEs were insomnia, decreased appetite, weight loss and irritability.Funding AcknowledgementsStudy sponsored by Sunovion Pharmaceuticals Inc.

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108 Lurasidone in Children and Adolescents With Bipolar Depression Presenting With Mixed Features

CNS Spectrums ◽

10.1017/s1092852918000081 ◽

2018 ◽

Vol 23 (1) ◽

pp. 70-70

Author(s):

Cynthia Siu ◽

Andrei Pikalov ◽

Michael Tocco ◽

Antony Loebel

Keyword(s):

Children And Adolescents ◽

Effect Size ◽

Repeated Measures ◽

Mixed Model ◽

Rating Scale ◽

Bipolar Depression ◽

Depression Score ◽

Double Blind ◽

Increased Risk ◽

Mixed Features

AbstractObjectiveTo evaluate the efficacy and safety of lurasidone in the treatment of children and adolescents with bipolar depression presenting with mixed features.MethodsPatients 10 to 17 years of age, inclusive, with a DSM-IV-TR diagnosis of bipolar I depression, were randomized to 6 weeks of double-blind treatment with once-daily, flexible doses of lurasidone 20-80 mg or placebo. The presence of mixed features (subthreshold hypomanic symptoms) was defined as a YMRS score > 5 at study baseline. Efficacy analyses included change from baseline to week 6 in Children Depression Rating Scale, Revised (CDRS-R) score (the primary outcome), and Clinical Global Impressions, Bipolar Severity of Depression Score (CGI-BP-S), using mixed model for repeated measures (MMRM) analysis.ResultsAt baseline, mixed features were present in 54.2% of patients (lurasidone, n=97/173; placebo, n=89/170). Treatment with lurasidone (vs placebo) was associated with significantly greater reductions in CDRS-R scores at week 6 in the mixed features group (-21.5 vs -15.9; P<0.01; effect size, 0.45), and in the group without mixed features (-20.4 vs -14.8; P<0.01; effect size, 0.45). Likewise, lurasidone was associated with greater effect size (vs placebo) for reductions inCGI-BP-S scores at week 6 in the mixed features group (-1.6 vs -1.1; P<0.001; effect size 0.57), and in the group without mixed features (-1.3 vs -1.0; P=0.05; effect size 0.30). Rates of protocol-defined treatment-emergent hypomania or mania were similar for lurasidone and placebo in patients with mixed features(lurasidone 8.2% vs. placebo 9.0%) and without mixed features (lurasidone 1.3% vs. placebo 3.7%).ConclusionsIn this post-hoc analysis, lurasidone was found to be efficacious for treating child and adolescent patients with bipolar depression presenting with mixed features(assessed cross-sectionally at study baseline). There was no increased risk of treatment-emergent mania observed in patients with or without mixed features.Funding AcknowledgementsSunovion Pharmaceuticals Inc.

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First use of cenerimod, a selective S1P1 receptor modulator, for the treatment of SLE: a double-blind, randomised, placebo-controlled, proof-of-concept study

Lupus Science & Medicine ◽

10.1136/lupus-2019-000354 ◽

2019 ◽

Vol 6 (1) ◽

pp. e000354 ◽

Cited By ~ 10

Author(s):

Viktoria Hermann ◽

Anastas Batalov ◽

Svetlana Smakotina ◽

Pierre-Eric Juif ◽

Peter Cornelisse

Keyword(s):

Lymphocyte Count ◽

Activity Index ◽

Plasma Concentrations ◽

Total Lymphocyte Count ◽

Controlled Study ◽

Double Blind ◽

Once Daily ◽

Receptor Modulator ◽

Total Lymphocyte ◽

Dsdna Antibodies

ObjectiveTo investigate the pharmacodynamics, pharmacokinetics and safety of cenerimod—a potent, oral, selective sphingosine 1-phosphate 1 receptor modulator—in patients with SLE.MethodsThis multicentre, double-blind, placebo-controlled study was conducted in two parts. In part A, patients with SLE were randomised 1:1:1:1 to receive oral cenerimod 0.5, 1 or 2 mg, or placebo once daily for 12 weeks. Following an interim safety review of part A, additional patients were randomised 3:1 for part B and received cenerimod 4 mg or placebo once daily for 12 weeks. Endpoints included changes in total lymphocyte count, SLE Disease Activity Index-2000 (SLEDAI-2K) score (modified (mSLEDAI-2K) to exclude leucopenia), biomarker anti-double-stranded DNA (anti-dsDNA) antibodies, pharmacokinetic assessments and treatment-emergent adverse events (TEAEs).ResultsPart A included 49 patients (1:1:1:1 receiving cenerimod 0.5, 1 or 2 mg, or placebo) and part B included 18 patients (13 cenerimod; 5 placebo). Cenerimod caused a statistically significant dose-dependent reduction in total lymphocyte count from baseline to end of treatment (EOT). Compared with placebo at EOT, cenerimod 4 mg had an estimated treatment effect on change from baseline in mSLEDAI-2K score of −2.420 (p=0.0306), and on anti-dsDNA antibodies of −64.55 U/mL (p=0.0082), suggesting clinical and biological improvement in these exploratory efficacy analyses. Trough plasma concentrations were dose proportional and reached steady-state conditions after 4 weeks of once daily dosing. All groups reported similar, non-dose-related frequencies of TEAEs (cenerimod 0.5 mg: 41.7%; 1 mg: 41.7%; 2 mg: 46.2%; 4 mg: 38.5% and placebo: 58.8%). A small, dose-related, non-clinically relevant decrease in heart rate was only observed in the first 6 hours after initiation.ConclusionsWith an acceptable safety profile, the efficacy findings suggest that cenerimod has the potential to treat patients with SLE. Further investigation in larger patient populations with longer treatment duration is warranted.

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Evaluation of At-home Bleaching Times on Effectiveness and Sensitivity with 10% Hydrogen Peroxide: A Randomized Controlled Double-blind Clinical Trial

Operative Dentistry ◽

10.2341/20-104-c ◽

2021 ◽

Author(s):

K Chemin ◽

M Rezende ◽

MC Costa ◽

ADY Salgado ◽

JL de Geus ◽

...

Keyword(s):

Clinical Trial ◽

Hydrogen Peroxide ◽

Repeated Measures ◽

Rating Scale ◽

Double Blind ◽

Tooth Sensitivity ◽

Once Daily ◽

Whitney Test ◽

Mann Whitney Test ◽

At Home

SUMMARY Objectives: The aim of this randomized double-blind controlled clinical trial was to evaluate different protocols for at-home use of 10% hydrogen peroxide in whitening effectiveness and tooth sensitivity. Methods: Seventy-two patients were selected according to the inclusion and exclusion criteria, with the upper central incisors having color A2 or darker according to the Vita Classical scale (VITA Zahnfabrik, Bad Säckingen, Germany) and randomized into two groups: 10% hydrogen peroxide applied once daily for 15 minutes (HP 15) or applied once daily for 30 minutes (HP 30). Bleaching was performed for 14 days in both groups. The color was evaluated before bleaching, during bleaching (1st and 2nd weeks), and 1 month after the bleaching treatment using the Vita Classical, Vita Bleachedguide 3D-MASTER, and Vita Easyshade spectrophotometer (VITA Zahnfabrik). Dental sensitivity was recorded by the patients using the numerical rating scale (0–4) and visual analogue scale (0-10 cm). Color data were evaluated by two-way analysis of variance (ANOVA) of repeated measures (group vs. treatment time). The Mann-Whitney test was performed to contrast the means (α=0.05). Tooth sensitivity was assessed by Fisher’s exact test (p=1.00) and intensity of tooth sensitivity was evaluated by the Mann-Whitney test (α=0.05) for both scales. Results: A significant whitening effect was observed after 2 weeks of bleaching for all color measurements (p=0.01), with no difference between HP 15 and HP 30 (p>0.05). Also, the absolute risk and intensity of tooth sensitivity were similar (47%; p>0.05). Conclusions: The effectiveness and tooth sensitivity of at-home bleaching carried out with 10% hydrogen peroxide applied for 15 minutes or 30 minutes are similar.

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113 Dasotraline for the Treatment of Moderate to Severe Binge Eating Disorder in Adults: Results From a Randomized, Double-Blind, Placebo-Controlled Study

CNS Spectrums ◽

10.1017/s1092852918000135 ◽

2018 ◽

Vol 23 (1) ◽

pp. 72-73 ◽

Cited By ~ 3

Author(s):

Bradford Navia ◽

James I. Hudson ◽

Susan L McElroy ◽

Anna I. Guerdjikova ◽

Ling Deng ◽

...

Keyword(s):

Placebo Group ◽

Eating Disorder ◽

Binge Eating ◽

Binge Eating Disorder ◽

Repeated Measures ◽

Plasma Concentrations ◽

Controlled Study ◽

Obsessive Compulsive ◽

Double Blind ◽

Secondary Endpoints

AbstractObjectivesBinge eating disorder (BED) is the most common eating disorder in the US, with a lifetime prevalence of 2.8%. Disturbances in reward circuitry have been implicated in its pathogenesis. Dasotraline is a novel and potent dopamine and norepinephrine reuptake inhibitor with slow absorption and a long half-life resulting in stable plasma concentrations over 24 hours with once-daily dosing. This study evaluated the efficacy and safety of flexibly-dosed dasotraline (4, 6, and 8 mg/day) vs placebo in adults with moderate to severe BED over a 12-week period (NCT02564588).MethodsKey inclusion criteria included moderate to severe BED based on a history of ≥2 binge eating days/week for ≥6 months prior to screening, and ≥3 binge eating days for each of2 weeks prior to randomization, as documented in participant’s binge eating diary. Patients were randomized 1:1 to flexibly-dosed dasotraline (4, 6, 8 mg/day) or placebo. Theprimary endpoint was change from baseline (CFB) in the number of binge eating days per week at Week 12. Key secondary endpoints were: CFB in Clinical Global Impression–Severity (CGI-S) Scale at Week 12; CFB in Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (YBOCS-BE) at Week 12; and the percentage ofsubjects with a 4-week cessation from binge eating prior to Week 12 or end of treatment (EOT). Except for 4-week cessation, the other three variables were analyzed using amixed model for repeated measures (MMRM).Results317 subjects (84% female) received ≥1 dose of study medication (mean age was 38.2 years; mean number of binge eating days per week, 4.25; mean CGI-S score, 4.5; mean BMI, 34.7). The MMRM analysis of CFB at Week 12 in the number of binge days/week yielded a significant mean difference of –0.99 (95% CI: –0.65 to –1.33; p<0.001) infavour of dasotraline (–3.74 in the dasotraline group vs –2.75 in the placebo group). All three key secondary endpoints were met at Week 12 or EOT: 46.5% of subjects in thedasotraline group achieved at least 4 consecutive weeks’ cessation from binge eating vs 20.6% in the placebo group (p<0.001); CFB in CGI-S and YBOCS-BE scores were also statistically significant in favour of dasotraline (p<0.001). The treatment-emergent adverse events (TEAEs) that occurred more frequently with dasotraline vs placebo at >2% incidence included: insomnia (44.6% vs 8.1%), dry mouth (27.4% vs 5.0%), decreased appetite (19.7% vs 6.9%), anxiety (17.8% vs 2.5%), nausea (12.7% vs 6.9%) and decreased body weight (12.1% vs 0%). Discontinuation due to AEs occurred in 11.5% of patients taking dasotraline vs 2.5% taking placebo.ConclusionsIn adults with moderate to severe BED, there were highly significant and clinically meaningful reductions with dasotraline vs placebo in the frequency of binge eating, global severity of illness, and obsessive-compulsive symptoms related to binge eating. These results suggest dasotraline may offer a novel, well-tolerated and efficacious treatmentfor BED.Funding AcknowledgementsStudy sponsored by Sunovion Pharmaceuticals Inc.

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A double-blind placebo-controlled study of brexpiprazole for the treatment of borderline personality disorder

The British Journal of Psychiatry ◽

10.1192/bjp.2021.159 ◽

2021 ◽

pp. 1-6

Author(s):

Jon E. Grant ◽

Stephanie Valle ◽

Eve Chesivoir ◽

Dustin Ehsan ◽

Samuel R. Chamberlain

Keyword(s):

Borderline Personality Disorder ◽

Personality Disorder ◽

Repeated Measures ◽

Rating Scale ◽

Safety Data ◽

Borderline Personality ◽

Small Sample ◽

Controlled Study ◽

Double Blind ◽

Double Blind Placebo

Background Borderline personality disorder is associated with impaired quality of life and has a number of untoward public health associations. There is no established first-line pharmacological treatment for borderline personality disorder, and available options are not suitable for all individuals. Aims To evaluate brexpiprazole, which has effects on the dopaminergic and serotonergic systems, for the reduction of borderline personality disorder symptoms. Method Eighty adults with borderline personality disorder were recruited for a randomised, double-blind placebo-controlled study. Participants received 12-week treatment with brexpiprazole (1 mg/day for 1 week, then increasing to 2 mg/day) or placebo in a parallel design. The primary efficacy outcome measure was the clinician-rated Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD). Safety data were collected. Effects of active versus placebo treatment were characterised with linear repeated measures models. Results There was a significant interaction between treatment and time on the ZAN-BPD scale (P = 0.0031), solely because of differentiation specifically at week 12. Brexpiprazole was generally well tolerated. Secondary measures did not result in statistically significant differences from placebo. Conclusions Brexpiprazole appears to have some possible effect on borderline personality disorder symptoms, but further studies are needed because of the significant effects evident, specifically at the final time point. These findings also need to be viewed cautiously, given the small sample size, large drop-out rate and robust placebo response.

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A fixed-dose randomized controlled trial of olanzapine for psychosis in Parkinson disease

F1000Research ◽

10.12688/f1000research.2-150.v1 ◽

2013 ◽

Vol 2 ◽

pp. 150 ◽

Cited By ~ 18

Author(s):

Michelle J Nichols ◽

Johanna M Hartlein ◽

Meredith GA Eicken ◽

Brad A Racette ◽

Kevin J Black

Keyword(s):

Parkinson Disease ◽

Repeated Measures ◽

Rating Scale ◽

Controlled Trial ◽

Depression Score ◽

Fixed Dose ◽

Drug Induced ◽

Serious Adverse Events ◽

Double Blind ◽

Significant Difference

Background: Psychosis is a common and debilitating side effect of long-term dopaminergic treatment of Parkinson disease (PD). While clozapine is an effective treatment, the need for blood monitoring has limited its first-line use. Objective: Since olanzapine shows similar receptor affinity to clozapine, we hypothesized that it might be an effective alternative to clozapine for treatment of drug-induced psychosis (DIP) in PD, and that lower doses than usual might make it tolerable.Methods: In 1998-2003 we conducted a four-week, double-blind, placebo-controlled, parallel group, fixed-dose trial of olanzapine (0, 2.5mg, or 5mg) in 23 PD patients with DIP while allowing for clinically realistic dose adjustments of dopaminomimetic mid-study. The primary outcome measures were Brief Psychiatric Rating Scale (BPRS) ratings scored from videotaped interviews after study termination by an observer blinded to dose assignment and to interview timing, and CGI (Clinical Global Impression). The Unified Parkinson’s Disease Rating Scale motor subscale (UPDRS) was the primary measure of tolerability.Results: Intention-to-treat analysis found no significant differences among treatment groups in study completion or serious adverse events. However, a disproportionate number of olanzapine vs. placebo subjects reported mild side effects (p<0.04), many citing motor worsening. Fourteen patients completed the study (seven on placebo, two on 2.5mg olanzapine, five on 5mg olanzapine). In study completers, analysis by repeated measures ANOVA revealed no significant difference between olanzapine and placebo groups in BPRS psychosis reduction (p=0.536), parkinsonism (p=0.608), or any other measured parameters (CGI, MMSE, Beck Depression Inventory, Hamilton Depression score, PDQ‑39, Schwab-England ADL assessment, and sleep scores).Conclusion: This study adds to other evidence that olanzapine is ineffective in treating medication-induced psychosis in Parkinson disease.

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

CNS Spectrums ◽

10.1017/s1092852917000232 ◽

2017 ◽

Vol 22 (2) ◽

pp. 228-235 ◽

Cited By ~ 5

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.

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Abstract T P121: A Comparative Study of Duloxetine and Paroxetine in Japanese Patients With Post-Stroke Depression

Stroke ◽

10.1161/str.45.suppl_1.tp121 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Shuji Matsumoto ◽

Megumi Shimodozono

Keyword(s):

Rating Scale ◽

Standard Dose ◽

Japanese Patients ◽

Fixed Dose ◽

Controlled Study ◽

Double Blind ◽

Post Stroke ◽

Significant Difference ◽

Post Stroke Depression ◽

Pain Symptoms

Background and methods: Patients with stroke may suffer from post-stroke depression and concomitant pain symptoms. A double-blind, parallel-group, controlled study was performed to investigate if duloxetine was superior to paroxetine in terms of improvement in symptoms of depression and pain in Japanese patients with post-stroke depression in a fixed-dose design. The efficacy and safety of duloxetine 60 mg/day were also assessed in comparison with those at the standard dose of 40 mg/day. Results: Changes in 17-item Hamilton depression rating scale (HAM-D) total score (mean ± standard deviation) for group D1 (duloxetine 40 mg/day), group M2 (duloxetine 60 mg/day), and group PX (paroxetine 20 mg/day) were –14.9 ± 5.6, –15.6 ± 6.4, and –11.4 ± 6.2, respectively, and the estimated differences in total score for group PX (Dunnett’s 95% simultaneous confidence interval) were 3.8 (3.2 to 4.4) for group D1 and 4.2 (3.6 to 4.8) for group D2. The superiority of groups M1 and M2 to group PX was thus confirmed, because the upper confidence limit of differences between groups D1 and PX and between groups D2 and PX was more than 3.2. The groups M1 and M2 presented a reduction in the pain, which was not observed in the group PX. The incidence of treatment-related adverse events was 21% for group D1, 28% for group D2, and 30% for group PX, indicating no significant difference between the three groups. Conclusion: These results demonstrate that duloxetine 40 mg/day and 60 mg/day is superior to paroxetine in terms of efficacy on post-stroke depression and central pain.

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Effect of losartan and spironolactone on triglyceride-rich lipoproteins in diabetic nephropathy

Journal of Investigative Medicine ◽

10.1136/jim-2016-000102 ◽

2016 ◽

Vol 64 (6) ◽

pp. 1102-1108 ◽

Cited By ~ 3

Author(s):

Anand Srivastava ◽

Beverley Adams-Huet ◽

Gloria L Vega ◽

Robert D Toto

Keyword(s):

Diabetic Nephropathy ◽

Repeated Measures ◽

Mixed Model ◽

Plasma Lipids ◽

Angiotensin Receptor Blockers ◽

Controlled Trial ◽

Low Density ◽

Double Blind ◽

Apo B ◽

Once Daily

Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) can improve dyslipidemia in patients with diabetes and albuminuria. Whether combined ACEi+ARB or ACEi+mineralocorticoid receptor blockade improves dyslipidemia is not known. We hypothesized long-term administration of either losartan 100 mg or spironolactone 25 mg once daily added onto lisinopril 80 mg once daily would improve dyslipidemia in diabetic nephropathy (DN). We measured lipid levels, very-low-density (V), intermediate-density (I), low-density (LDL), high-density (HDL) lipoprotein, LDL particle size with their respective cholesterol (C) and apolipoprotein B levels (ApoB), and urine albumin/creatinine ratio (UACR) at 12-week interval during a 48-week randomized, double-blind placebo-controlled trial in 81 patients with DN. Plasma lipids and lipoprotein C were analyzed enzymatically and Apo B was determined chemically. Data were analyzed by mixed model repeated measures. ΔUACR differed among treatment arms (placebo −24.6%, los −38.2%, spiro −51.6%, p=0.02). No correlation existed between ΔUACR and ΔTG or any of the lipid or lipoprotein measurements. Compared with placebo losartan, but not spironolactone, decreased TG (−20.9% vs +34.3%, p<0.01), V+I C(−18.8% vs +21.3%, p<0.01), and V+I-ApoB (−13.2% vs +21%, p<0.01). There were no significant changes in body weight, HbA1c or other lipoprotein variables. We conclude losartan improves dyslipidemia in patients with DN. We speculate the mechanism improved clearance of VLDL and remnant lipoproteins.Trial registration numberNCT00381134; Results.

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

BMC Neurology ◽

10.1186/s12883-021-02196-7 ◽

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).

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