Search

Background: The goal of the study was to assess the safety and tolerability of atogepant, an oral, calcitonin gene-related peptide receptor antagonist in development for migraine preventive treatment, once daily over 1 year. Methods: Multicenter, open-label trial (NCT03700320). Adults with migraine were randomized 5:2 to atogepant or oral standard-of-care (SOC) migraine prevention. Results: 744 randomized participants (n=546 atogepant), 739 safety population participants (n=543 atogepant). Adverse events (AEs) were reported by 67.0% of atogepant participants; 18.0% had AEs considered related to atogepant. AEs reported by ≥5% of atogepant-treated participants were upper respiratory tract infection (10.3%), constipation (7.2%), nausea (6.3%), and urinary tract infection (5.2%). 4.4% of atogepant participants reported serious AEs that included various, common medical conditions; no event occurred in ≥1 participant and none were atogepant-related. Two deaths were reported in atogepant-treated participants (homicide victim; toxic shock syndrome); both were considered not treatment-related. 5.7% of atogepant participants discontinued due to AEs. Alanine aminotransferase/aspartate aminotransferase levels ≥3X upper limit of normal were reported for 2.4% of atogepant participants (n=13/531) and 3.2% of SOC participants (n=6/190). No cases of potential Hy’s Law were reported. Conclusions: Once-daily use of atogepant for preventive treatment of migraine over 1 year was safe and well-tolerated with no safety concerns identified.

Background: Phase 3 PREEMPT established safety and efficacy of 155-195U onabotulinumtoxinA in adults with chronic migraine (CM). This analysis of the PREDICT study (NCT02502123) evaluates real-world effectiveness and safety of 155U, 156-195U and 195U-onabotulinumtoxinA in CM. Methods: Patients received onabotulinumtoxinA approximately every 12-weeks (≤7 treatment cycles [Tx]) per Canadian product monograph). Primary endpoint was mean change from baseline in Migraine-Specific Quality of Life (MSQ) at Tx4. Headache days, physician and patient satisfaction were evaluated. Analysis stratified safety population (≥1 onabotulinumtoxin A dose) into 3 groups (155U,156-195U,195U) by dose received on ≥3 of the first 4 Tx. Results: 184 patients received ≥1 onabotulinumtoxin A dose (155U, n=68; 156-195U, n=156; 195U, n=13 on ≥3 Tx). Headache days decreased over time compared to baseline (Tx4: -7.1[6.7] 155U; -6.5[6.7] 156-195U; -11.2[6.4] 195U). Physicians rated most patients as improved, and majority of patients were satisfied at final visit (80.8% 155U; 83.6% 156-195U; 90% 195U). Treatment-emergent adverse events (TEAEs) were reported in 18/68(26.5%) patients in 155U-group, 41/65(63.1%) in 156-195U-group and 10/13(76.9%) in 195U-group; treatment-related TEAEs were 9(13.2%), 10(15.4%) and 3(23.1%) respectively; serious TEAEs were 0, 3(4.6%) and 1(7.7%), none treatment-related. Conclusions: Long-term treatment with 155U, 156-195U, and 195U-onabotulinumtoxinA in PREDICT was safe and effective CM treatment. No new safety signals were identified.

Background: The goal of the study was to assess responder rates at various times after initiating atogepant treatment. Methods: A 12-week phase 3 trial evaluated the safety, efficacy, and tolerability of atogepant for preventive treatment of migraine (ADVANCE; NCT03777059) in adult participants with a ≥1-year history of migraine, experiencing 4-14 migraine days/month. Participants were randomized to atogepant 10, 30, or 60mg, or placebo once daily. These analyses evaluated ≥25%, ≥50%, ≥75%, and 100% reductions in mean monthly migraine days (MMDs) across 12 weeks and each 4-week interval. Adverse events (AEs) in ≥5% of participants are reported. Results: The efficacy analysis population included 873 participants: placebo: n=214; atogepant: 10mg: n=214; 30mg: n=223; 60mg: n=222. Atogepant-treated participants were more likely to experience a ≥50% reduction in the 3-month mean MMDs (56-61% vs 29% with placebo; PConclusions: Once-daily atogepant 10, 30, and 60mg significantly increased responder rates at all thresholds with approximately 60% achieving a ≥50% reduction in mean MMDs at 12 weeks.

Background: To evaluate efficacy, safety, and tolerability of ubrogepant, an oral CGRP receptor antagonist, for acute treatment of a single migraine attack. Methods: Multicenter, randomized, double-blind, placebo-controlled, parallel-group, single-attack, phase 3 study (NCT02828020). Patients randomized 1:1:1 to placebo, ubrogepant 50mg, or ubrogepant 100mg had 60 days to treat one migraine attack (moderate/severe pain intensity). Co-primary efficacy endpoints: pain freedom 2 hours post initial dose and absence of most bothersome migraine-associated symptom (MBS). Results: 1672 patients were randomized (safety population: n=1436; mITT population: n=1327). Mean age: 40.7 years; white (82.4%); female (87.5%). A significantly greater percentage of ubrogepant- than placebo-treated patients achieved pain freedom 2 hours post initial dose (50mg: 19.2%, adjusted P=0.0023; 100mg: 21.2%, adjusted P=0.0003; placebo: 11.8%). A significantly greater percentage of ubrogepant patients achieved absence of MBS (50mg: 38.6%, adjusted P=0.0023, 100mg: 37.7%, adjusted P=0.0023; placebo: 27.8%). The adverse event (AE) profile of ubrogepant was similar to placebo. The most common AEs (incidence ≥2% in any treatment group) within 48 hours of initial or optional second dose were nausea, somnolence, and dry mouth (all with incidence Conclusions: Both co-primary endpoints were met, with clinically meaningful effects on migraine headache pain and MBS. Ubrogepant was well tolerated, with no identified safety concerns.

Background: The clinical benefit of onabotulinumtoxinA in cervical dystonia (CD) is proven, but its impact on health-related quality of life (HRQoL) is largely unknown. Methods: Multicentre, prospective, observational study (NCT01655862) of CD patients treated with onabotulinumtoxinA at physician discretion (maximum 9 treatments). Patient-reported HRQoL outcomes and work productivity were collected at baseline, 4- or 8-weeks post-treatment, and final visit (prior to 9th treatment). OnabotulinumtoxinA utilization was assessed. Results: 61 patients received ≥1 treatment; 74.1% completed all treatments. Average total dose/treatment was 186.9U. The splenius capitis was most frequently treated (100% patients). Average pain numeric rating scale score was significantly improved at final visit (2.1) versus baseline (4.6; pConclusions: Long-term use of onabotulinumtoxinA is a safe, effective treatment for CD, improving HRQoL and work productivity.

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.