scholarly journals Long-term safety and tolerability of erenumab: Three-plus year results from a five-year open-label extension study in episodic migraine

Cephalalgia ◽  
2019 ◽  
Vol 39 (11) ◽  
pp. 1455-1464 ◽  
Author(s):  
Messoud Ashina ◽  
Peter J Goadsby ◽  
Uwe Reuter ◽  
Stephen Silberstein ◽  
David Dodick ◽  
...  
Keyword(s):  
Adverse Events ◽  
Vital Signs ◽  
Clinical Trial Data ◽  
Treatment Phase ◽  
Episodic Migraine ◽  
Upper Respiratory Tract ◽  
Open Label ◽  
Long Term Study ◽  
Open Label Extension

Background Previously published three-month placebo-controlled and one-year open-label clinical trial data have provided information on the efficacy and safety of erenumab. Methods Interim analysis was undertaken from an ongoing five-year open-label treatment phase after all patients completed three years in the open-label treatment phase or discontinued the study. Adult patients with episodic migraine enrolled in the open-label treatment phase initially received 70 mg erenumab monthly. A protocol amendment increased the dosage to 140 mg monthly to assess long-term safety of the higher dose. Safety and tolerability were assessed by monitoring adverse events, electrocardiograms, laboratory assessments, and vital signs. Results Of 383 patients enrolled in the open-label treatment phase, at data cutoff 235 (61.3%) remained in the study, all received 140 mg for ≥1 year. Median (Q1, Q3) exposure (70 or 140 mg) for all patients enrolled was 3.2 (1.3, 3.4) years. The most frequent adverse events (≥4.0/100 patient-years) were reported as viral upper respiratory tract infection, sinusitis, influenza, and back pain. Exposure-adjusted serious adverse event rates were 4.2/100 patient-years. There was no increase in cardiovascular events over time. Conclusions In this long-term study of a CGRP-receptor antibody, erenumab was found to be safe and well-tolerated with a spectrum and rate of adverse events consistent with shorter-term placebo-controlled studies. Trial registration ClinicalTrials.gov NCT01952574

scholarly journals Two-year efficacy and safety of erenumab in participants with episodic migraine and 2–4 prior preventive treatment failures: results from the LIBERTY study

2021 ◽  
pp. jnnp-2021-327480
Author(s):  
Michel Dominique Ferrari ◽  
Uwe Reuter ◽  
Peter J Goadsby ◽  
Gabriel Paiva da Silva Lima ◽  
Subhayan Mondal ◽  
...  
Keyword(s):  
Treatment Phase ◽  
Preventive Treatment ◽  
Episodic Migraine ◽  
Responder Rate ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Open Label Extension ◽  
Registration Number

ObjectiveTo evaluate individual and group long-term efficacy and safety of erenumab in individuals with episodic migraine (EM) for whom 2–4 prior preventatives had failed.MethodsParticipants completing the 12-week double-blind treatment phase (DBTP) of the LIBERTY study could continue into an open-label extension phase (OLEP) receiving erenumab 140 mg monthly for up to 3 years. Main outcomes assessed at week 112 were: ≥50%, ≥75% and 100% reduction in monthly migraine days (MMD) as group responder rate and individual responder rates, MMD change from baseline, safety and tolerability.ResultsOverall 240/246 (97.6%) entered the OLEP (118 continuing erenumab, 122 switching from placebo). In total 181/240 (75.4%) reached 112 weeks, 24.6% discontinued, mainly due to lack of efficacy (44.0%), participant decision (37.0%) and adverse events (AEs; 12.0%). The ≥50% responder rate was 57.2% (99/173) at 112 weeks. Of ≥50% responders at the end of the DBTP, 36/52 (69.2%) remained responders at ≥50% and 22/52 (42.3%) at >80% of visits. Of the non-responders at the end of the DBTP, 60/185 (32.4%) converted to ≥50% responders in at least half the visits and 24/185 (13.0%) converted to ≥50% responders in >80% of visits. Change from baseline at 112 weeks in mean (SD) MMD was −4.2 (5.0) days. Common AEs (≥10%) were nasopharyngitis, influenza and back pain.ConclusionsEfficacy was sustained over 112 weeks in individuals with difficult-to-treat EM for whom 2–4 prior migraine preventives had failed. Erenumab treatment was safe and well tolerated, in-line with previous studies.Trial registration numberNCT03096834

scholarly journals 134 Long-Term Deutetrabenazine Treatment Is Associated with Sustained Treatment Response in Tardive Dyskinesia: Results from an Open-Label Extension Study

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 284-285 ◽  
Author(s):  
Robert A. Hauser ◽  
Hadas Barkay ◽  
Hubert H. Fernandez ◽  
Stewart A. Factor ◽  
Joohi Jimenez-Shahed ◽  
...  
Keyword(s):  
Adverse Events ◽  
Percentage Change ◽  
Extension Study ◽  
Total Daily Dose ◽  
Open Label ◽  
Daily Dose ◽  
Open Label Extension ◽  
The Mean ◽  
Over Time

Abstract:Background:In the 12-week ARM-TD and AIM-TD studies evaluating deutetrabenazine for the treatment of tardive dyskinesia (TD), the percentage of patients achieving ≥50% response was higher in the deutetrabenazine-treated group than in the placebo group. These studies also showed low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine. The current open-label study evaluated the long-term efficacy and safety of deutetrabenazine in patients with TD.Methods:Patients with TD who completed ARM-TD or AIM-TD could enroll in this open-label, single-arm extension study, titrating up over 6 weeks to a maximum total daily dose of deutetrabenazine 48 mg/day on the basis of dyskinesia control and tolerability. The proportion of Abnormal Involuntary Movement Scale (AIMS; items 1-7) responders was assessed based on response rates for achieving ≥50% improvement from baseline in the open-label extension study. AlMS score was assessed by local site raters for this analysis.Results:343 patients enrolled in the extension study. At Week 54 (n=249; total daily dose [mean ± standard error]: 38.6±0.66 mg), the mean percentage change from baseline in AIMS score was –40%; 48% of patients achieved a ≥50% response and 59% of those had already achieved a ≥50% response at Week 15. Further, 34% of those who had not achieved a ≥50% response at Week 15 achieved a ≥50% response at Week 54. At Week 106 (n=169; total daily dose: 39.6±0.77 mg), the mean percentage change from baseline in AIMS score was –45%; 55% of patients achieved a ≥50% response, 59% of those patients had already achieved a ≥50% response at Week 15, and 41% of those who had not achieved a ≥50% response at Week 15 but who reached Week 106 achieved a ≥50% response. At Week 132 (n=109; total daily dose: 39.7±0.97 mg), the mean percentage change from baseline in AIMS score was –61%; 55% of patients achieved a ≥50% response, 61% of those patients had already achieved a ≥50% response at Week 15, and 43% of those who had not achieved a ≥50% response at Week 15 but who reached Week 132 achieved a ≥50% response. Completer analysis suggests that long-term efficacy was not due to dose increases over time. Treatment with deutetrabenazine was generally well tolerated. There were 623 patient-years of exposure through Week 158, and exposure-adjusted incidence rates (incidence/patient-years) of adverse events of special interest were 0.01 for akathisia and restlessness, 0.07 for somnolence and sedation, 0.04 for parkinsonism, and 0.05 for depression.Conclusions:Patients who received long-term treatment with deutetrabenazine achieved response rates that were indicative of clinically meaningful long-term benefit. Results from this open-label trial suggest the possibility of increasing benefit over time with individual dose titration of deutetrabenazine.Funding Acknowledgements:This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel.

scholarly journals 096 Assessment of the efficacy of erenumab during the open-label treatment (13–24 weeks) of subjects with episodic migraine who failed 2–4 prior preventive treatments: results of the LIBERTY study

2019 ◽  
Vol 90 (e7) ◽  
pp. A31.1-A31
Author(s):  
Lauren Giles ◽  
Uwe Reuter ◽  
Peter Goadsby ◽  
Michel Lanteri-Minet ◽  
Peggy Hours-Zesiger ◽  
...  
Keyword(s):  
Treatment Phase ◽  
Preventive Treatment ◽  
Episodic Migraine ◽  
Open Label ◽  
Double Blind ◽  
Open Label Extension ◽  
Specific Medication ◽  
Continuous Use ◽  
To Receive ◽  
Headache Impact

IntroductionTo assess efficacy of erenumab in the first three months of the open-label extension phase (OLEP; 13–24 weeks) of the LIBERTY study.MethodsIn the double-blind treatment phase (DBTP), 246 patients were randomized to placebo and erenumab 140 mg for 12 weeks, following which, patients completing that phase (N=240) were enrolled in OLEP, to receive monthly erenumab 140 mg. Outcomes measured monthly throughout to week 24 were achievement of at least 50%/75%/100% reduction in monthly migraine days (MMD), change from DBTP baseline in MMD, monthly acute migraine-specific medication days (MSMD), Headache Impact Test (HIT-6TM) total score, everyday activities (EA) and physical impairment (PI) as measured by the Migraine Physical Function Impact Diary (MPFID).ResultsOverall, 228/240(95.0%) patients completed the 24 week visit of the OLEP. In the overall population at Week 24, 39.2%, 15.9% and 7.0% patients achieved ≥50%/≥75%/100% reduction in MMD. The mean (standard deviation) change from DBTP baseline in MMD was −2.7(4.4) and −1.4(3.0) in MSMD; and −7.6(8.0), −2.5(9.2) and −4.0(9.0) in HIT-6TM, MPFID-PI and MPFID-EA scores respectively. Patients with continuous use of erenumab showed sustained efficacy in all outcomes assessed. Patients who switched from placebo to erenumab in the OLEP showed improvement from the first measurement at Week 16 on all outcomes assessed.ConclusionsEfficacy of erenumab was sustained throughout 24 weeks in a hard to treat patient population with multiple prior preventive treatment failures. Overall, efficacy data over 24 weeks (assessed over weeks 13–16,17–20 and 21–24) was generally in line with prior erenumab trials.

scholarly journals Safety and effectiveness of lurasidone in adolescents with schizophrenia: results of a 2-year, open-label extension study

CNS Spectrums ◽  
2020 ◽  
pp. 1-11
Author(s):  
Christoph U. Correll ◽  
Robert L. Findling ◽  
Michael Tocco ◽  
Andrei Pikalov ◽  
Ling Deng ◽  
...  
Keyword(s):  
Body Weight ◽  
Adverse Events ◽  
Rating Scales ◽  
Extension Study ◽  
Open Label ◽  
Double Blind ◽  
Syndrome Scale ◽  
Open Label Extension ◽  
Glycemic Indices

Abstract Background Minimal long-term benefit: Risk data are available regarding antipsychotic treatments for schizophrenia in pediatric populations. This study evaluated the long-term safety, tolerability, and effectiveness of lurasidone in adolescents with schizophrenia. Methods Patients aged from 13 to 17 who completed 6 weeks of double-blind (DB), placebo-controlled treatment with lurasidone were enrolled in a 2-year, open-label (OL), flexible dose (20-80 mg/day) lurasidone treatment study. Safety was assessed via spontaneous reporting, rating scales, body weight measurement, metabolic, and prolactin testing. Effectiveness measures included the Positive and Negative Syndrome Scale (PANSS) total score. Results About 271 patients completed 6 weeks of DB treatment and entered the 2-year OL extension study. Altogether, 42.4% discontinued prematurely, 10.7% due to adverse events. During OL treatment, the most common adverse events were headache (24.0%); anxiety (12.9%), schizophrenia, and nausea (12.5%); sedation/somnolence (12.2%); and nasopharyngitis (8.9%). Minimal changes were observed on metabolic parameters and prolactin. Mean change from DB baseline in weight at week 52 and week 104 was +3.3 kg and + 4.9 kg, respectively, compared to an expected weight gain of +3.4 kg and + 5.7 kg, respectively, based on the sex- and age-matched US Center for Disease Control normative data. Continued improvement was observed in PANSS total score, with mean change from OL baseline of −15.6 at week 52 and −18.4 at week 104. Conclusion In adolescents with schizophrenia, long-term lurasidone treatment was associated with minimal effects on body weight, lipids, glycemic indices, and prolactin. Continued improvement in symptoms of schizophrenia was observed over 2 years of lurasidone treatment.

scholarly journals 14 Long-term Efficacy of Brexpiprazole in Patients with Schizophrenia with Clinically Relevant Levels of Negative Symptoms

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 180-180
Author(s):  
Catherine Weiss ◽  
Peter Zhang ◽  
Ross A Baker ◽  
Mary Hobart ◽  
Nanco Hefting ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Extension Study ◽  
Short Term ◽  
Open Label ◽  
Term Study ◽  
Post Hoc Analysis ◽  
Long Term Study ◽  
Open Label Extension ◽  
Post Hoc

AbstractBackgroundEffective treatments for patients with high levels of negative symptoms of schizophrenia are lacking. Brexpiprazole is a serotonin–dopamine activity modulator that is a partial agonist at 5-HT1A and dopamine D2 receptors, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors, all with subnanomolar potency. Long-term treatment with brexpiprazole demonstrated broad efficacy across all five Marder factor groupings, including positive, negative, disorganized thoughts, uncontrolled hostility/excitement, and anxiety/depression. This post-hoc analysis of long-term effects of brexpiprazole in patients with clinically relevant levels of negative symptoms of schizophrenia is based on data from two similarly designed short-term, placebo-controlled studies (Vector; NCT01396421 or Beacon; NCT01393613) for the brexpiprazole-treated patients who continued into an open-label extension study (Zenith; NCT01397786).MethodsIn the short-term studies, patients with acute schizophrenia were randomly assigned to fixed once-daily doses of brexpiprazole 0.25mg (Vector), 1mg (Beacon), 2mg , 4mg or placebo for 6weeks. The long-term study was an open-label, 52-week (amended to 26weeks), safety extension study with flexible-dose (1–4mg/day) brexpiprazole. The post-hoc analyses were performed on brexpiprazole-treated patients from the short-term studies who continued into the long-term study, and who had clinically relevant negative symptoms, defined as PANSS Factor Score for Negative Symptoms (PANSS-FSNS; N1, N2, N3, N4, G7, G16) of ≥24, and score of ≥4 on at least two of three core negative symptom PANSS items at randomization in the parent study. The outcome of the analysis included change from baseline to up to 58weeks in PANSS-FSNS, PANSS Total, and PSP. Safety was also assessed.ResultsA total of 187 patients with clinically relevant levels of negative symptoms in the parent study rolled-over into the open-label extension study and were available for analysis. Eighty-three of these patients remained in the studies for 58weeks. Due to the study amendment, not all patients had the opportunity of complete 52weeks of open-label treatment. Baseline PANSS Total score was 104.4, while baseline PANSS-FSNS was 27.6 and baseline PSP Total score was 41.3. Mean change (SD) from baseline in PANSS-FSNS was –10.9 (5.0), and –44.2 (17.5) for PANSS Total score at Week 58. Change from baseline (SD) to Week 58 for PSP Total score was 24.8 (12.9) with improvement in all domains (socially useful activities, personal and social relationship, self-care, and disturbing and aggressive behaviors). The TEAEs reported ≥5% were schizophrenia (18.9%), insomnia (8.6%), weight increased (5.9%) and akathisia (5.9%).ConclusionThis post-hoc analysis suggests that brexpiprazole has long-term effectiveness on negative symptoms and functioning in patients with schizophrenia and clinically relevant levels of negative symptoms.Funding Acknowledgements: The study was funded by Otsuka Pharmaceutical Development & Commercialization Inc. and H. Lundbeck A/S

scholarly journals A Long-Term, Open-Label, Safety Study of Triple-Bead Mixed Amphetamine Salts (SHP465) in Adults With ADHD

2017 ◽  
Vol 24 (3) ◽  
pp. 434-446 ◽  
Author(s):  
Lenard A. Adler ◽  
Glen Frick ◽  
Brian Yan
Keyword(s):  
Rating Scale ◽  
Symptom Control ◽  
Vital Signs ◽  
Early Morning ◽  
Dose Titration ◽  
Open Label ◽  
Diagnostic And Statistical Manual ◽  
Open Label Extension ◽  
Higher Doses

Objective: The aim of this study was to evaluate the long-term safety of triple-bead mixed amphetamine salts (MAS) in adults with ADHD. Method: Adults meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR) ADHD criteria and satisfying study criteria from one of two antecedent studies were enrolled in this 52-week (dose titration, 4 weeks; dose maintenance, 11 months) open-label extension. The protocol included 12.5- to 75-mg triple-bead MAS but was amended to a maximum of 50-mg triple-bead MAS. Safety evaluations included treatment-emergent adverse events (TEAEs) and vital signs. Clinical outcome measures included ADHD Rating Scale–IV (ADHD-RS-IV) total score changes. Results: Of 505 enrolled participants, 266 completed the study; the M ± SD daily dose during the study was 48.0 ± 15.96 mg. The most frequent TEAEs were insomnia (initial insomnia, insomnia, early morning awakening, middle insomnia; 38.2%), headache (25.7%), and dry mouth (20.2%). Study discontinuations were more frequent with higher doses of triple-bead MAS (37.5-75 mg) than with lower doses (12.5 and 25 mg). Blood pressure and pulse increases were observed at end-of-study. Mean ADHD-RS-IV total score decreases from antecedent study and open-label baselines at end-of-study were −23.3 ± 11.44 and −7.9 ± 13.19, respectively. Conclusion: Triple-bead MAS exhibited a long-term safety profile comparable with previous reports and demonstrated evidence of continued symptom control for up to 12 months.

One-Year Open-Label Safety and Efficacy Study of Paliperidone Extended-Release Tablets in Patients With Schizophrenia

CNS Spectrums ◽  
2010 ◽  
Vol 15 (8) ◽  
pp. 506-514 ◽  
Author(s):  
Michelle Kramer ◽  
George Simpson ◽  
Valentinas Maciulis ◽  
Stuart Kushner ◽  
Yanning Liu ◽  
...  
Keyword(s):  
Adverse Events ◽  
Extended Release ◽  
Tolerability Profile ◽  
Open Label ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Stabilization Phase ◽  
Open Label Extension ◽  
Paliperidone Extended Release

ABSTRACTIntroduction: This 52-week open-label extension (OLE) to a double-blind placebo-controlled recurrence prevention study examined the long-term safety and efficacy of flexibly-dosed paliperidone extended-release (ER) tablets in patients with schizophrenia.Methods: Patients entering the OLE either entered from the double-blind phase (placebo or paliperidone ER treatment) or entered directly from the run-in or stabilization phase (paliperidone ER) of the earlier study. During the OLE, patients were treated with flexibly-dosed paliperidone ER (3–15 mg/day; 9 mg starting dose). Safety and tolerability assessments included incidence of adverse events and extrapyramidal symptoms. Efficacy was also assessed.Results: The study population (n=235) was predominantly men (66%), 18–58 years of age. Twelve patients (5%) experienced an adverse event requiring treatment discontinuation. One or more serious treatment-emergent adverse events were reported in 13 patients (6%). There was one death. The mean Positive and Negative Syndrome Scale total score decreased from open-label baseline to endpoint for all groups, regardless of previous double-blind treatment (placebo or paliperidone ER).Conclusion: This year-long OLE provides information on the long-term safety and tolerability of paliperidone ER in patients with schizophrenia. The resulting safety and tolerability profile was similar to that seen in earlier short-term studies.

Erenumab (AMG 334) in episodic migraine

Neurology ◽  
2017 ◽  
Vol 89 (12) ◽  
pp. 1237-1243 ◽  
Author(s):  
Messoud Ashina ◽  
David Dodick ◽  
Peter J. Goadsby ◽  
Uwe Reuter ◽  
Stephen Silberstein ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Safety Data ◽  
Preventive Treatment ◽  
Episodic Migraine ◽  
Controlled Clinical Trial ◽  
Open Label ◽  
Double Blind ◽  
Open Label Extension

Objective:To assess long-term safety and efficacy of anti–calcitonin gene-related peptide receptor erenumab in patients with episodic migraine (EM).Methods:Patients enrolled in a 12-week, double-blind, placebo-controlled clinical trial (NCT01952574) who continued in an open-label extension (OLE) study will receive erenumab 70 mg every 4 weeks for up to 5 years. This preplanned interim analysis, conducted after all participants had completed the 1-year open-label follow-up, evaluated changes in monthly migraine days (MMD), achievement of ≥50%, ≥75%, and 100% reductions, Headache Impact Test (HIT-6) score, Migraine-Specific Quality of Life (MSQ), Migraine Disability Assessment (MIDAS), and safety. Data reported as observed without imputation for missing data.Results:Of 472 patients enrolled in the parent study, 383 continued in the OLE with a median exposure to erenumab of 575 days (range 28–822 days). Mean (SD) MMD were 8.8 (2.6) at parent study baseline, 6.3 (4.2) at week 12 (beginning of OLE), and 3.7 (4.0) at week 64 (mean change from baseline [reduction] of 5.0 days). At week 64, 65%, 42%, and 26% achieved ≥50%, ≥75%, and 100% reduction in MMD, respectively. Mean HIT-6 scores were 60.2 (6.3) at baseline and 51.7 (9.2) at week 64. MSQ and MIDAS improvements from baseline were maintained through week 64. Safety profiles during the OLE were similar to those in the double-blind phase, which overall were similar to placebo.Conclusions:One-year efficacy, supported by functional improvements and favorable safety and tolerability profiles, supports further investigation of erenumab as a preventive treatment in patients with EM.Clinicaltrials.gov identifier:NCT01952574.Classification of evidence:This study provides Class IV evidence that for patients with episodic migraine, erenumab reduces long-term MMD and improves headache-related disability and migraine-specific quality of life.

Long-term safety and efficacy of erenumab in patients with chronic migraine: Results from a 52-week, open-label extension study

Cephalalgia ◽  
2020 ◽  
Vol 40 (6) ◽  
pp. 543-553 ◽  
Author(s):  
Stewart J Tepper ◽  
Messoud Ashina ◽  
Uwe Reuter ◽  
Jan Lewis Brandes ◽  
David Doležil ◽  
...  
Keyword(s):  
Adverse Event ◽  
Chronic Migraine ◽  
Treatment Phase ◽  
Extension Study ◽  
Open Label ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Open Label Extension ◽  
Event Rates

Background This study reports the long-term safety and efficacy of erenumab in chronic migraine patients. Methods This was a 52-week open-label extension study of a 12-week double-blind treatment phase study. During the double-blind treatment phase, patients received placebo or once-monthly erenumab 70 mg or 140 mg. During the open-label treatment phase, the initial monthly dose was erenumab 70 mg. Following protocol amendment, patients continued to receive erenumab 70 mg if they had already completed their Week 28 visit, otherwise, patients switched from 70 mg to 140 mg; if enrolled after the amendment, patients received 140 mg monthly throughout. Results In all, 451/609 (74.1%) enrolled patients completed the study. The exposure-adjusted patient incidence rate for any adverse event was 126.3/100 patient-years for the overall erenumab group. Overall, the adverse event profile was similar to that observed in the double-blind treatment phase. Adverse event incidence rates did not increase with long-term erenumab treatment compared with the double-blind treatment phase, and no new serious or treatment-emergent events were seen. Efficacy was sustained throughout the 52 weeks. Clinically significant reductions from double-blind treatment phase baseline (about half) were observed for monthly migraine days and migraine-specific medication days. Achievement of ≥50%, ≥75% and 100% reductions from the double-blind treatment phase baseline in monthly migraine days at Week 52 were reported by 59.0%, 33.2% and 8.9% of patients, respectively, for the combined dose group. A numerically greater benefit was observed with 140 mg compared with 70 mg at Weeks 40 and 52. Conclusions Sustained efficacy of long-term erenumab treatment in patients with chronic migraine is demonstrated, with safety results consistent with the known safety profile of erenumab and adverse event rates comparable to placebo adverse event rates in the double-blind treatment phase. Trial registration: This study is registered at ClinicalTrials.gov (NCT02174861)

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