scholarly journals P.032 Long-term safety and tolerability of eptinezumab in patients with chronic migraine: A 2-year, open-label, phase 3 trial

2021 ◽  
Vol 48 (s3) ◽  
pp. S29-S29
Author(s):  
D Kudrow ◽  
R Cady ◽  
B Allan ◽  
S Pederson ◽  
J Hirman ◽  
...  
Keyword(s):  
Adverse Events ◽  
Chronic Migraine ◽  
Patient Reported Outcomes ◽  
Drug Discontinuation ◽  
Upper Respiratory Tract ◽  
Open Label ◽  
Phase 3 ◽  
Patient Reported ◽  
Open Label Phase

Background: Eptinezumab is approved in the US for the preventive treatment of migraine and was well tolerated in double-blind, placebo-controlled studies in patients with episodic and chronic migraine (CM). The PREVAIL study evaluated the long-term safety, immunogenicity, and impact on patient-reported outcomes of repeat doses of eptinezumab in patients with CM. Methods: PREVAIL was an open-label, phase 3 trial comprising two 48-week treatment phases. Adults with CM received eptinezumab 300 mg by 30-minute IV every 12 weeks for ≤8 doses, with patients followed up to week 104. Results: 128 adults (mean age, 41.5y) with CM were treated. Over 2 years, the most frequently reported treatment-emergent adverse events were nasopharyngitis (14.1%), upper respiratory tract infection (7.8%), sinusitis (7.8%), influenza (6.3%), bronchitis (5.5%), and migraine (5.5%). Study-drug discontinuation due to adverse events was 6.3%. Anti-eptinezumab antibody incidence peaked at week 24 and declined despite continued dosing, to nondetectable levels at week 104. Patient-reported outcomes were improved at first assessment (week 4) and generally sustained through week 104. Conclusions: In adults with CM, eptinezumab 300 mg demonstrated a favorable safety profile, limited long-term immunogenicity, early and sustained reductions in migraine-related burden, and improvements in health-related quality of life over 2 years.

scholarly journals Long-term safety and tolerability of eptinezumab in patients with chronic migraine: a 2-year, open-label, phase 3 trial

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
David Kudrow ◽  
Roger K. Cady ◽  
Brent Allan ◽  
Susan M. Pederson ◽  
Joe Hirman ◽  
...  
Keyword(s):  
Adverse Events ◽  
Chronic Migraine ◽  
Patient Reported Outcomes ◽  
Treatment Phase ◽  
The United States ◽  
Open Label ◽  
Phase 3 ◽  
Patient Reported ◽  
Open Label Phase

Abstract Background Eptinezumab, an anti-calcitonin gene-related peptide monoclonal antibody recently approved in the United States for preventive treatment of migraine in adults, was found to be well tolerated in double-blind, placebo-controlled studies in patients with episodic and chronic migraine. The objective of the PREVAIL study was to evaluate the long-term safety, immunogenicity, and impact on patient-reported outcomes of repeat doses of eptinezumab in patients with chronic migraine. Methods PREVAIL was an open-label, phase 3 trial comprising a 48-week treatment phase followed by a second 48-week treatment phase. Adults with chronic migraine received eptinezumab 300 mg by 30-min intravenous administration every 12 weeks for up to 8 doses. Patients were followed for 20 weeks after the final infusion (end-of-study visit at week 104). Results Overall, 128 adults (mean age, 41.5 years) with chronic migraine were included. During the 2 years, the most frequently reported treatment-emergent adverse events were nasopharyngitis (14.1%), upper respiratory tract infection (7.8%), sinusitis (7.8%), influenza (6.3%), bronchitis (5.5%), and migraine (5.5%). The rate of study-drug discontinuation due to adverse events was 6.3%, which included 3 patients with infusion-related hypersensitivity. The incidence of anti-eptinezumab antibodies peaked at week 24 and declined despite continued dosing, to nondetectable levels at week 104. Improvements in patient-reported outcomes were observed at first assessment (week 4) and generally sustained through week 104. Conclusion In adults with chronic migraine, eptinezumab 300 mg demonstrated a favorable safety profile, limited long-term immunogenicity, early and sustained reductions in migraine-related burden, and improvements in health-related quality of life over 2 years. Trial registration ClinicalTrials.gov (Identifier: NCT02985398).

scholarly journals 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 ◽  
2019 ◽  
Vol 39 (11) ◽  
pp. 1343-1357 ◽  
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

scholarly journals Long-term safety and efficacy of lasmiditan for acute treatment of migraine: Final results of the GLADIATOR study

2020 ◽  
Vol 3 ◽  
pp. 251581632095817
Author(s):  
Jan Lewis Brandes ◽  
Suzanne Klise ◽  
John H Krege ◽  
Michael Case ◽  
Rashna Khanna ◽  
...  
Keyword(s):  
Adverse Events ◽  
Interim Analysis ◽  
Acute Treatment ◽  
Episodic Migraine ◽  
Migraine Treatment ◽  
Open Label ◽  
Phase 3 ◽  
Post Dose ◽  
Open Label Phase

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.

scholarly journals Patient-Reported Outcomes from a Randomized, Active-Controlled, Open-Label, Phase 3 Trial of Burosumab Versus Conventional Therapy in Children with X-Linked Hypophosphatemia

2021 ◽  
Author(s):  
Raja Padidela ◽  
Michael P. Whyte ◽  
Francis H. Glorieux ◽  
Craig F. Munns ◽  
Leanne M. Ward ◽  
...  
Keyword(s):  
Physical Function ◽  
Conventional Therapy ◽  
Patient Reported Outcomes ◽  
Fibroblast Growth Factor 23 ◽  
Pain Interference ◽  
Measurement Information ◽  
Open Label ◽  
Phase 3 ◽  
Patient Reported ◽  
Open Label Phase

AbstractChanging to burosumab, a monoclonal antibody targeting fibroblast growth factor 23, significantly improved phosphorus homeostasis, rickets, lower-extremity deformities, mobility, and growth versus continuing oral phosphate and active vitamin D (conventional therapy) in a randomized, open-label, phase 3 trial involving children aged 1–12 years with X-linked hypophosphatemia. Patients were randomized (1:1) to subcutaneous burosumab or to continue conventional therapy. We present patient-reported outcomes (PROs) from this trial for children aged ≥ 5 years at screening (n = 35), using a Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire and SF-10 Health Survey for Children. PROMIS pain interference, physical function mobility, and fatigue scores improved from baseline with burosumab at weeks 40 and 64, but changed little with continued conventional therapy. Pain interference scores differed significantly between groups at week 40 (− 5.02, 95% CI − 9.29 to − 0.75; p = 0.0212) but not at week 64. Between-group differences were not significant at either week for physical function mobility or fatigue. Reductions in PROMIS pain interference and fatigue scores from baseline were clinically meaningful with burosumab at weeks 40 and 64 but not with conventional therapy. SF-10 physical health scores (PHS-10) improved significantly with burosumab at week 40 (least-squares mean [standard error] + 5.98 [1.79]; p = 0.0008) and week 64 (+ 5.93 [1.88]; p = 0.0016) but not with conventional therapy (between-treatment differences were nonsignificant). In conclusion, changing to burosumab improved PRO measures, with statistically significant differences in PROMIS pain interference at week 40 versus continuing with conventional therapy and in PHS-10 at weeks 40 and 64 versus baseline.Trial registration: ClinicalTrials.gov NCT02915705

OnabotulinumtoxinA for treatment of chronic migraine: Results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial

Cephalalgia ◽  
2010 ◽  
Vol 30 (7) ◽  
pp. 804-814 ◽  
Author(s):  
HC Diener ◽  
DW Dodick ◽  
SK Aurora ◽  
CC Turkel ◽  
RE DeGryse ◽  
...  
Keyword(s):  
Adverse Events ◽  
Chronic Migraine ◽  
Primary Efficacy ◽  
Primary Efficacy Endpoint ◽  
Efficacy And Safety ◽  
Open Label ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Open Label Phase

Objectives: This is the second of a pair of studies designed to evaluate the efficacy and safety of onabotulinumtoxinA (BOTOX®) for prophylaxis of headaches in adults with chronic migraine. Methods: PREEMPT 2 was a phase 3 study, with a 24-week, double-blind, placebo-controlled phase, followed by a 32-week, open-label phase. Subjects were randomized (1:1) to injections of onabotulinumtoxinA (155U–195U; n = 347) or placebo ( n = 358) every 12 weeks for two cycles. The primary efficacy endpoint was mean change in headache days per 28 days from baseline to weeks 21–24 post-treatment. Results: OnabotulinumtoxinA was statistically significantly superior to placebo for the primary endpoint, frequency of headache days per 28 days relative to baseline (−9.0 onabotulinumtoxinA/−6.7 placebo, p < .001). OnabotulinumtoxinA was significantly favoured in all secondary endpoint comparisons. OnabotulinumtoxinA was safe and well tolerated, with few treatment-related adverse events. Few patients (3.5% onabotulinumtoxinA/1.4% placebo) discontinued due to adverse events. Conclusions: The results of PREEMPT 2 demonstrate that onabotulinumtoxinA is effective for prophylaxis of headache in adults with chronic migraine. Repeated onabotulinumtoxinA treatments were safe and well tolerated.

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