A multicenter, open-label, long-term safety and tolerability study of DFN-02, an intranasal spray of sumatriptan 10 mg plus permeation enhancer DDM, for the acute treatment of episodic migraine

GLADIATOR was a prospective, randomized, open-label, phase 3 study of lasmiditan 100 mg or 200 mg dosed intermittently for up to 1 year in patients with episodic migraine. Most patients had completed one of two single-attack studies before participation. A total of 2030 patients received ≥1 lasmiditan dose and 19,879 migraine attacks were treated. Safety results were similar to the previously reported interim analysis. The most frequently reported treatment-emergent adverse events (TEAEs) included dizziness (18.5%), somnolence (8.5%), and paresthesia (6.8%), with frequency of adverse events appearing to decrease with subsequently treated attacks. At 2 h post-dose, 26.7% and 32.2% of all attacks treated with lasmiditan 100 mg and 200 mg, respectively, were pain free. This pattern was generally consistent across study quarters and treated attacks. In conclusion, during a 1-year treatment period, intermittent lasmiditan for episodic migraine treatment was associated with generally decreasing TEAEs and consistent efficacy.

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Open-Label Long-Term Safety Study of AXS-07 for the Acute Treatment of Migraine

Case Medical Research ◽

10.31525/ct1-nct04068051 ◽

2019 ◽

Author(s):

Keyword(s):

Acute Treatment ◽

Open Label ◽

Safety Study

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Long-Term, Open-Label Safety Study of Oral Almotriptan 12.5 mg for the Acute Treatment of Migraine in Adolescents

Headache The Journal of Head and Face Pain ◽

10.1111/j.1526-4610.2010.01655.x ◽

2008 ◽

Vol 50 (5) ◽

pp. 795-807 ◽

Cited By ~ 8

Author(s):

Frank Berenson ◽

Elza Vasconcellos ◽

Ann Pakalnis ◽

Lian Mao ◽

David M. Biondi ◽

...

Keyword(s):

Acute Treatment ◽

Open Label ◽

Safety Study

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

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2021-327480 ◽

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

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Long-Term Open-Label Safety Study of Rizatriptan Acute Treatment in Pediatric Migraineurs

Headache The Journal of Head and Face Pain ◽

10.1111/j.1526-4610.2012.02285.x ◽

2012 ◽

Vol 53 (1) ◽

pp. 104-117 ◽

Cited By ~ 10

Author(s):

David J. Hewitt ◽

Eric Pearlman ◽

Mirja Hämäläinen ◽

Donald Lewis ◽

Kathryn M. Connor ◽

...

Keyword(s):

Acute Treatment ◽

Open Label ◽

Safety Study

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Erenumab (AMG 334) in episodic migraine

Neurology ◽

10.1212/wnl.0000000000004391 ◽

2017 ◽

Vol 89 (12) ◽

pp. 1237-1243 ◽

Cited By ~ 83

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.

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Long term safety, tolerability, and efficacy of intracutaneous zolmitriptan (M207) in the acute treatment of migraine

The Journal of Headache and Pain ◽

10.1186/s10194-021-01249-z ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Stephanie J. Nahas ◽

Nada Hindiyeh ◽

Deborah I. Friedman ◽

Nada Elbuluk ◽

Donald J. Kellerman ◽

...

Keyword(s):

Adverse Events ◽

Migraine Attack ◽

Acute Treatment ◽

Application Site ◽

Tolerability Profile ◽

Open Label ◽

Post Dose ◽

Link Type ◽

Repeated Use

Abstract Objective To determine the long-term safety and tolerability profile of M207 in the acute treatment of migraine. Background M207 is an investigational microneedle-based system for intracutaneous delivery of zolmitriptan for the treatment of migraine attacks. Following on the positive results of a Phase 2/3 placebo-controlled efficacy study (ZOTRIP), this study was designed to evaluate the safety of this novel product during repeated use for the treatment of migraine attacks. Methods In this 6–12 month open-label, multicenter observational study, participants used an eDiary to record headache symptoms and adverse events at specified intervals up to 48 h following treatment of a qualifying attack with M207 3.8 mg (intracutaneous zolmitriptan). Participants underwent clinical evaluations at specified intervals up to 12 months. Results Among 335 participants who treated ≥1 migraine attack, 257 completed 6 months and 127 completed 1 year of treatment. The most common reason for withdrawal from the study was a low frequency of reported attacks post randomization. Overall, 5963 migraine attacks were treated. Most participants (96%) experienced at least 1 adverse event, the vast majority of which concerned the application site, and > 95% of which were mild. Fifteen participants (4%) withdrew due to adverse events; 4 withdrew due to 7 application site reactions, 6 of which were mild. Participants achieved pain freedom in 2477/5617 (44%) of attacks, most bothersome symptom freedom in 3315/5330 (62%) of attacks, and pain relief 2 h post-dose in 4552/5617 (81%) of attacks. Sustained pain freedom 2–24 h was seen in 1761/4698 (38%) of attacks, and 2–48 h in 1534/4429 (35%) of attacks. Conclusions The majority of participants experienced cutaneous adverse reactions such as application site erythema, swelling, and bleeding, and most reactions were scored as mild. These results are consistent with what was observed in the single migraine attack treatment ZOTRIP trial indicating that M207 is well tolerated in the setting of longer-term repeated use. Efficacy findings were also similar to those in the ZOTRIP trial. Trial registration Clinicaltrials.gov on September 13, 2017 (NCT03282227).

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Interim results of a prospective, randomized, open-label, Phase 3 study of the long-term safety and efficacy of lasmiditan for acute treatment of migraine (the GLADIATOR study)

Cephalalgia ◽

10.1177/0333102419864132 ◽

2019 ◽

Vol 39 (11) ◽

pp. 1343-1357 ◽

Cited By ~ 16

Author(s):

Jan Lewis Brandes ◽

Suzanne Klise ◽

John H Krege ◽

Michael Case ◽

Rashna Khanna ◽

...

Keyword(s):

Adverse Events ◽

Acute Treatment ◽

Electronic Diary ◽

Open Label ◽

Phase 3 ◽

Post Dose ◽

Serious Adverse Events ◽

Long Term Study ◽

Open Label Phase

Objectives To address the need for long-term lasmiditan data, the GLADIATOR study evaluated the safety (primary) and efficacy (secondary) of lasmiditan for the intermittent, acute treatment of migraine attacks for up to 1 year. Methods In this prospective, randomized, open-label, Phase 3 study, patients who had completed either of two single-attack studies were offered the opportunity to be randomized 1:1 to lasmiditan 100 mg or 200 mg. Patients were asked to use lasmiditan as the first treatment for each new migraine attack of at least moderate severity. Assessments occurred at baseline and at prespecified time increments up to 48 hours after each dose of study drug using an electronic diary, and safety was assessed throughout the study. Migraine Disability Assessment (MIDAS) was assessed at each visit. Results As of the cut-off date for this interim analysis (6 March 2018), 1978 patients had received ≥ 1 lasmiditan dose and treated 19,058 migraine attacks. Overall, treatment-emergent adverse events (TEAEs) were similar to those in the single-attack studies and included dizziness (18.6%), somnolence (8.5%), and paresthesia (6.8%). The frequency of TEAEs generally decreased with subsequent attacks. No treatment-related serious adverse events and no cardiovascular TEAEs potentially due to vasoconstriction were observed. For both lasmiditan doses, efficacy measures were generally consistent over study quarters and treated attacks. Overall, across all treated attacks at 2 hours post-dose, pain freedom was observed in 26.9% of the attacks treated with lasmiditan 100 mg and 32.4% of the attacks treated with lasmiditan 200 mg. MIDAS total scores decreased over time. Conclusions The interim results of this long-term study showed intermittent lasmiditan (100 mg and 200 mg) to be generally well tolerated and efficacious for the acute treatment of migraine over a 1-year period. Trial registration number: NCT02565186; https://clinicaltrials.gov/ct2/show/NCT02565186

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Long‐term efficacy and safety during open‐label erenumab treatment in Japanese patients with episodic migraine

Headache The Journal of Head and Face Pain ◽

10.1111/head.14096 ◽

2021 ◽

Vol 61 (4) ◽

pp. 653-661

Author(s):

Fumihiko Sakai ◽

Takao Takeshima ◽

Yoshihisa Tatsuoka ◽

Koichi Hirata ◽

Sunfa Cheng ◽

...

Keyword(s):

Japanese Patients ◽

Episodic Migraine ◽

Efficacy And Safety ◽

Open Label ◽

Term Efficacy

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Reversion from chronic migraine to episodic migraine following treatment with erenumab: Results of a post-hoc analysis of a randomized, 12-week, double-blind study and a 52-week, open-label extension

Cephalalgia ◽

10.1177/0333102420973994 ◽

2020 ◽

pp. 033310242097399

Author(s):

Richard B Lipton ◽

Stewart J Tepper ◽

Stephen D Silberstein ◽

David Kudrow ◽

Messoud Ashina ◽

...

Keyword(s):

Confidence Interval ◽

Chronic Migraine ◽

Controlled Trial ◽

Treatment Phase ◽

Episodic Migraine ◽

Double Blind Study ◽

Open Label ◽

Double Blind ◽

Clinical Trial Registration

Objective To determine reversion rates from chronic migraine to episodic migraine during long-term erenumab treatment. Methods A daily headache diary was completed during the 12-week, double-blind treatment phase of a placebo-controlled trial comparing erenumab 70 mg, 140 mg, and placebo, and weeks 1–12, 21–24, 37–40, and 49–52 of the open-label treatment phase. Chronic migraine to episodic migraine reversion rates were assessed over the double-blind treatment phase; persistent reversion to episodic migraine over 24 weeks (double-blind treatment phase through the first 12 weeks in the open-label treatment phase), long-term persistent reversion to episodic migraine over 64 weeks (double-blind treatment phase plus open-label treatment phase); delayed reversion to episodic migraine through the first 12 weeks of the open-label treatment phase among patients remaining in chronic migraine during the double-blind treatment phase. Results In the double-blind treatment phase, 53.1% (95% confidence interval: 47.8–58.3) of 358 erenumab-treated completers had reversion to episodic migraine; monthly reversion rates to episodic migraine were typically higher among patients receiving 140 mg versus 70 mg. Among 181 completers (receiving erenumab for 64 weeks), 98 (54.1% [95% confidence interval: 46.6–61.6]) had reversion to episodic migraine during the double-blind treatment phase; of those, 96.9% (95% confidence interval: 91.3–99.4) had persistent reversion to episodic migraine, 96.8% (95% confidence interval: 91.1–99.3) of whom had long-term persistent reversion to episodic migraine. Delayed reversion to episodic migraine occurred in 36/83 (43.4% [95% confidence interval: 32.5–54.7]) patients; of these, 77.8% (95% confidence interval: 60.9–89.9) persisted in reversion through week 64. Conclusions Patients with reversion to episodic migraine at week 12 will likely persist as episodic migraine with longer-term erenumab; others may achieve delayed reversion to episodic migraine. Clinical trial registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02066415

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