Lasmiditan efficacy in the acute treatment of migraine was independent of prior response to triptans: Findings from the CENTURION study

Cephalalgia ◽  
2021 ◽  
pp. 033310242110485
Author(s):  
Uwe Reuter ◽  
John H Krege ◽  
Louise Lombard ◽  
Elisa Gomez Valderas ◽  
Judith Krikke-Workel ◽  
...  
Keyword(s):  
Pain Relief ◽  
Acute Treatment ◽  
Receptor Agonist ◽  
Rescue Medication ◽  
Significant Proportion ◽  
Phase 3 ◽  
Patient Global Impression ◽  
Insufficient Response ◽  
Bothersome Symptom ◽  
Global Impression Of Change

Background A significant proportion of triptan users exhibit an insufficient response or inadequate tolerability to a triptan, and some may develop a contraindication. Lasmiditan, a selective 5-HT1F receptor agonist, may be an option for these individuals. We assessed lasmiditan efficacy in a subgroup of patients in CENTURION (Phase 3 migraine consistency study) who exhibited an insufficient response to triptans, including a subgroup with insufficient response due to efficacy only. Methods Patients were randomized to lasmiditan 200 mg for four attacks, lasmiditan 100 mg for four attacks, or placebo for three and lasmiditan 50 mg for one attack. Triptan insufficient responders were pre-defined as patients with insufficient efficacy or tolerability, or who developed a contraindication. Results In triptan insufficient responders, lasmiditan was superior to placebo ( p < 0.05) for pain freedom beginning at 1 h (both doses); pain relief beginning at 0.5 (200 mg) or 1 h (100 mg); migraine-related disability freedom, much/very much better on the Patient Global Impression of Change, and most bothersome symptom freedom at 2 h; sustained pain freedom; and need for rescue medication. Lasmiditan showed benefit for consistency of effect across attacks for 2-h pain freedom and pain relief. Findings were similar in triptan responders and triptan naïve patients and when the triptan insufficient response definition was based on efficacy only. Conclusions Lasmiditan was efficacious across multiple clinically relevant endpoints in the acute treatment of migraine independent of prior response to triptans. Trial Registration: CENTURION (NCT03670810); SAMURAI (NCT02439320); SPARTAN (NCT02605174)

scholarly journals P.010 Efficacy, safety, and tolerability of ubrogepant for the acute treatment of migraine: a single-attack phase 3 study, ACHIEVE II

2019 ◽  
Vol 46 (s1) ◽  
pp. S16 ◽  
Author(s):  
RB Lipton ◽  
DW Dodick ◽  
J Ailani ◽  
K Lu ◽  
H Lakkis ◽  
...  
Keyword(s):  
Pain Relief ◽  
Acute Treatment ◽  
Statistical Significance ◽  
Phase 3 ◽  
Double Blind ◽  
Primary Endpoints ◽  
Safety Population ◽  
Secondary Endpoints ◽  
Attack Phase ◽  
Headache Pain

Background: To evaluate efficacy, safety, and tolerability of ubrogepant for acute treatment of migraine attacks. Methods: Multicenter, double-blind, phase 3 study (NCT02867709). Randomized patients (1:1:1, placebo or ubrogepant 25mg or 50mg) had 60 days to treat one migraine attack (moderate/severe pain intensity). Co-primary efficacy endpoints (2 hours post initial dose): headache pain freedom and absence of most bothersome migraine-associated symptom (MBS). Secondary endpoints: pain relief, sustained pain relief, sustained pain freedom, and absence of migraine-associated symptoms. Results: 1686 patients were randomized (safety population: n=1465; mITT population: n=1355). Mean age: 41 years; white: 81%; female: 89%. Significantly greater proportions of ubrogepant- than placebo-treated patients achieved 2-hour pain freedom (placebo: 14.3%; 25mg: 20.7%, adjusted P=0.0285; 50mg: 21.8%, adjusted P=0.0129) and absence of MBS for 50mg (placebo: 27.4%; 50mg: 38.9%, adjusted P=0.0129). Secondary endpoints (except absence of nausea at 2h) met statistical significance versus placebo for ubrogepant 50mg. Absence of MBS and secondary outcomes were not significant for 25mg after multiplicity adjustment. Ubrogepant’s and placebo’s AE profiles were similar. Conclusions: Co-primary endpoints were met for ubrogepant 50mg. Ubrogepant 25mg was significantly superior to placebo for 2h pain freedom. Ubrogepant was well tolerated. Results support the efficacy, tolerability, and safety of ubrogepant for acute treatment of migraine attacks.

scholarly journals Lasmiditan for the acute treatment of migraine: Subgroup analyses by prior response to triptans

Cephalalgia ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 19-27 ◽  
Author(s):  
Kerry Knievel ◽  
Andrew S Buchanan ◽  
Louise Lombard ◽  
Simin Baygani ◽  
Joel Raskin ◽  
...  
Keyword(s):  
Acute Treatment ◽  
Therapeutic Option ◽  
Placebo Treatment ◽  
Therapeutic Benefit ◽  
Comparable Efficacy ◽  
Significant Treatment ◽  
Subgroup Analyses ◽  
Insufficient Response ◽  
Bothersome Symptom ◽  
Headache Pain

Background Lasmiditan demonstrated superiority to placebo in the acute treatment of migraine in adults with moderate/severe migraine disability in two similarly designed Phase 3 trials, SAMURAI and SPARTAN. Post-hoc integrated analyses evaluated the efficacy of lasmiditan in patients who reported a good or insufficient response to triptans and in those who were triptan naïve. Methods Subgroups of patients reporting an overall response of “good” or “poor/none” to the most recent use of a triptan at baseline (defined as good or insufficient responders, respectively) and a triptan-naïve subpopulation were derived from combined study participants randomized to receive lasmiditan 50 mg (SPARTAN only), 100 mg or 200 mg, or placebo, as the first dose. Outcomes including headache pain-freedom, most bothersome symptom-freedom, and headache pain relief 2 hours post-first dose of lasmiditan were compared with placebo. Treatment-by-subgroup analyses additionally investigated whether therapeutic benefit varied according to prior triptan response (good or insufficient). Results Regardless of triptan response, lasmiditan showed higher efficacy than placebo (most comparisons were statistically significant). Treatment-by-subgroup analyses found that the benefit over placebo of lasmiditan did not vary significantly between patients with a good response and those with an insufficient response to triptans. Lasmiditan also showed higher efficacy than placebo in triptan-naïve patients. Conclusions Lasmiditan demonstrated comparable efficacy in patients who reported a good or insufficient response to prior triptan use. Lasmiditan also showed efficacy in those who were triptan naïve. Lasmiditan may be a useful therapeutic option for patients with migraine. Trial Registration SAMURAI (NCT02439320); SPARTAN (NCT02605174).

scholarly journals Effect of a rescue or recurrence dose of lasmiditan on efficacy and safety in the acute treatment of migraine: Findings from the Phase 3 trials (SAMURAI and SPARTAN)

2019 ◽  
Author(s):  
Li Shen Loo ◽  
Brian Plato ◽  
Ira Turner ◽  
Michael Case ◽  
Joel Raskin ◽  
...  
Keyword(s):  
Acute Treatment ◽  
Study Drug ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
Rescue Treatment ◽  
Patient Pain ◽  
Bothersome Symptom ◽  
Severe Migraine ◽  
Headache Recurrence

Abstract Background We studied the efficacy and safety of a second dose of lasmiditan for acute treatment of migraine. Methods SAMURAI and SPARTAN were double-blind, placebo-controlled Phase 3 studies in which individuals with migraine were randomized to oral lasmiditan 50mg (SPARTAN only), 100mg, 200mg, or placebo. Study drug was to be taken within 4 hours (h) of onset of a migraine attack (moderate or severe pain). A second dose of study drug was provided for rescue (patient not pain-free at 2h and took a second dose 2-24h post-first dose) or recurrence (patient pain-free at 2h, but experienced recurrence of mild, moderate, or severe migraine pain and took a second dose 2-24h after first dose). Randomization to second dose occurred at baseline; patients originally assigned lasmiditan were randomized to the same lasmiditan dose or placebo (2:1 ratio), and those originally assigned placebo received placebo. Data from SAMURAI and SPARTAN were pooled for efficacy and safety assessment of a second dose of lasmiditan. Results The proportion of patients taking a second dose was lower with lasmiditan versus placebo, and decreased with increasing lasmiditan dose; the majority who took a second dose did so for rescue. In patients taking lasmiditan as first dose, outcomes (pain free, most bothersome symptom [MBS] free) at 2h after a second dose for rescue were similar whether the second dose was lasmiditan or placebo (p>0.05 in all cases). In patients taking lasmiditan for first dose, outcomes at 2h after a second dose for recurrence were as follows: lasmiditan pooled versus placebo - pain free, 50% vs 32% (p>0.05); MBS free, 71% vs 41% (p=0.02); pain relief, 77% vs 52% (p=0.03). In patients whose first dose was lasmiditan, the incidence of treatment emergent adverse events (TEAEs) reported after the second dose was similar whether second dose was lasmiditan or placebo. Conclusions A second dose of lasmiditan showed some evidence of efficacy when taken for headache recurrence. There was no clear benefit of a second dose of lasmiditan for rescue treatment. The incidences of TEAEs were similar whether the second dose was lasmiditan or placebo.

scholarly journals Effect of a rescue or recurrence dose of lasmiditan on efficacy and safety in the acute treatment of migraine: Findings from the Phase 3 trials (SAMURAI and SPARTAN)

2019 ◽  
Author(s):  
Li Shen Loo ◽  
Brian Plato ◽  
Ira Turner ◽  
Michael Case ◽  
Joel Raskin ◽  
...  
Keyword(s):  
Acute Treatment ◽  
Study Drug ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
Rescue Treatment ◽  
Patient Pain ◽  
Bothersome Symptom ◽  
Severe Migraine ◽  
Headache Recurrence

Abstract Background We studied the efficacy and safety of a second dose of lasmiditan for acute treatment of migraine. Methods SAMURAI and SPARTAN were double-blind, placebo-controlled Phase 3 studies in which individuals with migraine were randomized to oral lasmiditan 50mg (SPARTAN only), 100mg, 200mg, or placebo. Study drug was to be taken within 4 hours (h) of onset of a migraine attack (moderate or severe pain). A second dose of study drug was provided for rescue (patient not pain-free at 2h and took a second dose 2-24h post-first dose) or recurrence (patient pain-free at 2h, but experienced recurrence of mild, moderate, or severe migraine pain and took a second dose 2-24h after first dose). Randomization to second dose occurred at baseline; patients originally assigned lasmiditan were randomized to the same lasmiditan dose or placebo (2:1 ratio), and those originally assigned placebo received placebo. Data from SAMURAI and SPARTAN were pooled for efficacy and safety assessment of a second dose of lasmiditan. Results The proportion of patients taking a second dose was lower with lasmiditan versus placebo, and decreased with increasing lasmiditan dose; the majority who took a second dose did so for rescue. In patients taking lasmiditan as first dose, outcomes (pain free, most bothersome symptom [MBS] free) at 2h after a second dose for rescue were similar whether the second dose was lasmiditan or placebo (p>0.05 in all cases). In patients taking lasmiditan for first dose, outcomes at 2h after a second dose for recurrence were as follows: lasmiditan pooled versus placebo - pain free, 50% vs 32% (p>0.05); MBS free, 71% vs 41% (p=0.02); pain relief, 77% vs 52% (p=0.03). In patients whose first dose was lasmiditan, the incidence of treatment emergent adverse events (TEAEs) reported after the second dose was similar whether second dose was lasmiditan or placebo. Conclusions A second dose of lasmiditan showed some evidence of efficacy when taken for headache recurrence. There was no clear benefit of a second dose of lasmiditan for rescue treatment. The incidences of TEAEs were similar whether the second dose was lasmiditan or placebo.

scholarly journals Eptinezumab for the prevention of chronic migraine: efficacy and safety through 24 weeks of treatment in the phase 3 PROMISE-2 (Prevention of migraine via intravenous ALD403 safety and efficacy–2) study

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Stephen Silberstein ◽  
Merle Diamond ◽  
Nada A. Hindiyeh ◽  
David M. Biondi ◽  
Roger Cady ◽  
...  
Keyword(s):  
Chronic Migraine ◽  
Patient Reported Outcomes ◽  
Controlled Study ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
Patient Global Impression ◽  
Calcitonin Gene ◽  
Patient Reported ◽  
Global Impression Of Change

Abstract Background PROMISE-2 was a phase 3, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of repeat intravenous (IV) doses of the calcitonin gene-related peptide–targeted monoclonal antibody eptinezumab (ALD403) for migraine prevention in adults with chronic migraine. This report describes the results of PROMISE-2 through 24 weeks of treatment. Methods Patients received up to two 30-min IV administrations of eptinezumab 100 mg, 300 mg, or placebo separated by 12 weeks. Patients recorded migraine and headache endpoints in a daily eDiary. Additional assessments, including patient-reported outcomes, were performed at regularly scheduled clinic visits throughout the 32-week study period (screening, day 0, and weeks 2, 4, 8, 12, 16, 20, 24, and 32). Results A total of 1072 adults received treatment: eptinezumab 100 mg, n = 356; eptinezumab 300 mg, n = 350; placebo, n = 366. The reduction in mean monthly migraine days observed during the first dosing interval (100 mg, − 7.7 days; 300 mg, − 8.2 days; placebo, − 5.6 days) was further decreased after an additional dose (100 mg, − 8.2 days; 300 mg, − 8.8 days; placebo, − 6.2 days), with both doses of eptinezumab demonstrating consistently greater reductions from baseline compared to placebo. The ≥50% and ≥ 75% migraine responder rates (MRRs) increased after a second dose, with more eptinezumab-treated patients experiencing migraine response than placebo patients (≥50% MRRs weeks 13–24: 100 mg, 61.0%; 300 mg, 64.0%; placebo, 44.0%; and ≥ 75% MRRs weeks 13–24: 100 mg, 39.3%; 300 mg, 43.1%; placebo, 23.8%). The percentages of patients who improved on patient-reported outcomes, including the Headache Impact Test and Patient Global Impression of Change, increased following the second dose administration at week 12, and were greater with eptinezumab than with placebo at all time points. No new safety concerns were identified with the second dose regarding the incidence, nature, and severity of treatment-emergent adverse events. Conclusion Eptinezumab 100 mg or 300 mg administered IV at day 0 and repeated at week 12 provided sustained migraine preventive benefit over a full 24 weeks and demonstrated an acceptable safety profile in patients with chronic migraine. Trial registration ClinicalTrials.gov (Identifier: NCT02974153). Registered November 23, 2016.

scholarly journals Acute treatment of migraine with external trigeminal nerve stimulation: A pilot trial

2019 ◽  
Vol 2 ◽  
pp. 251581631982990 ◽  
Author(s):  
Deena Kuruvilla ◽  
Joseph I Mann ◽  
Jean Schoenen ◽  
Sophie Penning
Keyword(s):  
Pain Relief ◽  
Outcome Measures ◽  
Trigeminal Nerve ◽  
Nerve Stimulation ◽  
Acute Treatment ◽  
Rescue Medication ◽  
Secondary Outcome ◽  
Trigeminal Nerve Stimulation ◽  
Associated Symptoms ◽  
At Home

Objective: The main objective of this study was to obtain efficacy data for external trigeminal nerve stimulation (e-TNS) in the acute treatment of migraine in patients using the device at home. Methods: This was a single-center, open-label trial conducted at the Rochester Clinical Research Center (Rochester, NY, USA). Patients who met International Classification of Headache Disorders, Third Edition, criteria for migraine with and without aura for ≥1 year and having between 2 and 8 moderate or severe attacks per month were recruited. Patients were advised to treat one migraine attack of moderate to severe intensity that started less than 4 h earlier and was not treated with an acute migraine medication, with a 2-h e-TNS session. Primary outcome measures were pain freedom at 2 h and most bothersome migraine-associated symptom (MBS) freedom at 2 h. Secondary outcome measures were pain relief at 2 h, the absence of migraine-associated symptoms at 2 h, the use of rescue medication between 2 and 24 h, and sustained pain freedom at 24 h. Results: Fifty-nine subjects were included in the study, and among them, 48 subjects were eligible for the modified intention-to-treat analysis. After 2 h of e-TNS, 35.4% of the subjects were pain-free, 60.4% were MBS-free, 70.8% had pain relief, and 45.8% were free from all migraine-associated symptoms. Half of the subjects took rescue medication between 2 h and 24 h, and sustained pain freedom at 24 h was achieved for 25.0% of the subjects. Regarding safety, 15 patients reported adverse events, all minor and fully reversible, mainly forehead paresthesia. Conclusions: This study shows that e-TNS with the Cefaly® Acute Device is effective, well-tolerated, and safe for the acute treatment of migraine in patients using the device at home. A large, multicenter, randomized, sham-controlled trial is needed to confirm this finding.

Spinal Cord Stimulation for Central Poststroke Pain

2010 ◽  
Vol 67 (3) ◽  
pp. ons206-ons212 ◽  
Author(s):  
Mohamed M. Aly ◽  
Youichi Saitoh ◽  
Koichi Hosomi ◽  
Satoru Oshino ◽  
Haruhiko Kishima ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Pain Relief ◽  
Spinal Cord Stimulation ◽  
Therapeutic Potential ◽  
Vas Score ◽  
Patient Global Impression ◽  
Global Impression Of Change ◽  
To Receive

Abstract BACKGROUND: Although spinal cord stimulation (SCS) has been shown to be effective for treating neuropathic pain of peripheral origin, its effectiveness for central poststroke pain (CPSP) is not well established. OBJECTIVE: We report our experience with SCS in 30 consecutive patients with intractable CPSP. METHODS: All patients underwent a percutaneous SCS trial. When patients decided to proceed, they received a permanent SCS system. Pain intensity was evaluated by a visual analogue scale (VAS). The Patient Global Impression of Change (PGIC) scale was also assessed at the latest follow-up visit as an indicator of overall improvement. RESULTS: During trial stimulation, pain relief was good (≥50% VAS score reduction) in 9 patients (30%), fair (30%–49% reduction) in 6 patients (20%), and poor (&lt;30% reduction) in 15 patients (50%). Ten patients elected to receive a permanent SCS system. Nine of these 10 patients were followed long-term (mean, 28 months; range, 6–62 months). Seven patients reported significant pain relief on the VAS (5 = good and 2 = fair). On the PGIC scale, 6 of these 7 patients reported a rating of 2 (much improved) and 1 reported a rating of 3 (minimally improved). Of the remaining 2 patients, 1 reported a rating of 4 (no change) and 1 reported a rating of 5 (minimally worse). The median VAS score in the 9 patients decreased significantly from 8.6 (range, 6.0–10.0) to 4.5 (range, 3.0–8.0; P= .008). There were no significant reported complications. CONCLUSION: SCS may provide improved pain control in a group of patients with intractable CPSP and may have therapeutic potential for intractable CPSP.

scholarly journals Time course of efficacy of ubrogepant for the acute treatment of migraine: Clinical implications

Cephalalgia ◽  
2020 ◽  
pp. 033310242097052
Author(s):  
Peter J Goadsby ◽  
Andrew M Blumenfeld ◽  
Richard B Lipton ◽  
David W Dodick ◽  
Kavita Kalidas ◽  
...  
Keyword(s):  
Pain Relief ◽  
Acute Treatment ◽  
Time Course ◽  
Plasma Concentrations ◽  
Pharmacokinetic Analysis ◽  
Maximum Plasma ◽  
Double Blind ◽  
Entire Time ◽  
Bothersome Symptom ◽  
Pharmacologically Active

Background The full utility of an acute treatment requires examination of the entire time course of effect during a migraine attack. Here the time course of effect of ubrogepant is evaluated. Methods ACHIEVE-I and -II were double-blind, single-attack, Phase 3 trials. Adults with migraine were randomised 1:1:1 to placebo or ubrogepant (50mg or 100mg, ACHIEVE-I; 25 mg or 50 mg, ACHIEVE-II). Pain freedom, absence of most bothersome symptom, and pain relief were assessed at various timepoints. Samples were collected for pharmacokinetic analysis. Data were pooled for this post-hoc analysis. Results Participants’ (n = 912 placebo, n = 887 ubrogepant 50 mg, pooled analysis population) mean age was 41 years, with a majority female and white. Pain relief separated from placebo by 1 h (43% versus 37% [OR, 95% CI: 1.30, 1.0–1.59]), absence of most bothersome symptom by 1.5 h (28% versus 22% [1.42, 1.14–1.77]), and pain freedom by 2 h (20% vs. 13% [1.72, 1.33–2.22]). Efficacy was sustained from 2–24 h (pain relief: 1.71, 1.1–2.6; pain freedom: 1.71, 1.3–2.3) and remained separated at 48 h (pain relief: 1.7, 1.1–2.6; pain freedom: 1.31, 1.0–1.7). Pharmacokinetic analysis demonstrated maximum plasma concentrations were achieved at 1 h, with pharmacologically active concentrations reached within 11 min and remaining above the EC90 for nearly 12 h. Conclusions Evaluation of the time course of effect of ubrogepant showed pain relief as the most sensitive and earliest measure of clinical effect, followed by absence of most bothersome symptom, and pain freedom. Efficacy was demonstrated out to 48 h, providing evidence of the long-lasting effect of ubrogepant. This evaluation supports the role of examining the entire time course of effect to understand fully the utility of an acute treatment for migraine. Trial registration: ACHIEVE I (ClinicalTrials.gov, NCT02828020) and ACHIEVE II (ClinicalTrials.gov, NCT02867709)

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