Rimegepant 75mg oral lyophilisates sugar free

BACKGROUND: Novel abortive treatments for migraine, ditans and gepants, have promising implications in triptan-insufficient responders with minimal existing comparative data. Our study aims to synthesize evidence through a systematic review and network meta-analysis to assess the comparative efficacy of lasmiditan, rimegepant and ubrogepant in triptan-insufficient responders. METHOD: We searched PubMed, Embase, CENTRAL, and EBSCO Open Dissertations up to May 2024. We included randomized controlled trials (RCTs) that compared novel abortive treatments, including lasmiditan, rimegepant, and ubrogepant, in migraine patients who self-reported insufficient response to triptans. Outcomes are represented using relative risks with corresponding 95% confidence intervals (CI). The surface under the cumulative ranking curve (SUCRA) was used to rank each medication. RESULTS: A total of five phase 3 RCTs involving 3,004 patients were included in the analysis. All three agents were significantly superior to placebo for two-hour pain freedom (RR = 1.93, 95% CI [1.52, 2.46]), freedom from the most bothersome symptoms at two hours (RR = 1.55, 95% CI [1.37, 1.75]), and pain relief at two hours (RR = 1.46, 95% CI [1.35, 1.58]). No statistically significant differences in efficacy outcomes were observed among the three agents. However, lasmiditan 200 mg had the highest cumulative probability for two-hour pain freedom and relief (SUCRA 0.9, 0.8, respective), while rimegepant led in relieving the most bothersome symptoms (SUCRA 0.7). CONCLUSION: Lasmiditan, rimegepant, and ubrogepant are effective for acute treatment of migraine in triptan-insufficient responders, with high-dose lasmiditan showing the highest efficacy for pain control.

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BACKGROUND: Rimegepant, a novel oral calcitonin gene-related peptide receptor antagonist, has been recently approved for the acute migraine treatment. While its efficacy was confirmed in randomized clinical trials, no data is available regarding real-life effectiveness and tolerability. GAINER, a prospective, multicentric study, aimed to evaluate rimegepant effectiveness and tolerability in the real-world setting. METHODS: Our study involved 16 headache centers across Italy. The main outcomes were: i) 2 h pain freedom, and ii) occurrence of treatment-emergent adverse events after administration. Participants were instructed to treat one migraine attack with rimegepant 75 mg orally disintegrating tablet. Using an ad hoc diary, participants prospectively collected migraine attack features at baseline and every 30 min after rimegepant administration, up to 2 h post dose. A 24 h follow up was also collected. RESULTS: We enrolled 103 participants with migraine (74.8% female, mean age 44.4 [42.0 - 46.7] years, 24.3% with chronic migraine of whom 44.0% presented a concomitant diagnosis of medication overuse headache). The number of previously failed preventive classes was 2.7 [2.3 - 3.2]. Participants presented a mean of 9.6 [8.2 - 10.9] monthly migraine days at baseline. At rimegepant intake, 40.8% of patients rated migraine intensity as severe. Pain freedom 2 h post dose was reported in 44.7% (46/103) of individuals. Pain freedom 2 h post dose was not influenced by baseline pain severity (p = 0.316), but it was associated with timing of intake (p = 0.032) with a higher rate of 2 h pain freedom when rimegepant was taken within 1 h from pain onset. Mild adverse events were reported in 15.5% total attacks (16/103), predominantly fatigue (n = 6), gastrointestinal symptoms (n = 6), somnolence (n = 4), and transient cognitive difficulties (n = 3). Tolerability was rated as good-to-excellent in 85.4% cases (88/103). CONCLUSIONS: Our data confirms rimegepant effectiveness and safety in the acute migraine treatment in a real-world setting in a cohort of participants that includes subjects with episodic or chronic migraine, medication overuse and a high number of prior preventive treatment failures. TRIAL REGISTRATION: The study was preregistered on clinicaltrial.gov, NCT05903027.

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OBJECTIVES/BACKGROUND: This study was undertaken to compare the efficacy of the oral calcitonin gene-related peptide receptor antagonist rimegepant relative to placebo as a preventive treatment for migraine in Japan. This was the first randomized placebo-controlled trial of rimegepant for the preventive treatment of migraine to be conducted outside the United States and the second conducted globally. METHODS: In this phase 3, double-blind, randomized, multicenter trial, conducted August 9, 2022 through January 18, 2024, adults in Japan with a history of 4-18 migraine attacks/month of moderate or severe pain intensity completed a 28-day observation phase and then took rimegepant 75 mg or placebo every other day during the 12-week double-blind treatment phase. The primary endpoint was the mean change from the observation phase in the number of monthly migraine days in the last 4 weeks of the double-blind treatment phase. Safety was assessed based on the frequency of adverse events and laboratory test abnormalities during the double-blind treatment phase. RESULTS: A total of 484 (efficacy) and 496 (safety) treated participants were evaluable. During the observation phase, participants in the rimegepant and placebo groups, respectively, reported a mean (SD) of 9.3 (3.1) and 9.0 (3.1) monthly migraine days. The study met its primary endpoint with a statistically significant difference in mean change from the observation phase in the number of monthly migraine days in the last 4 weeks of the double-blind treatment phase (difference rimegepant vs. placebo: -1.1 [95% confidence interval = -1.73 to -0.38], p = 0.002). In the rimegepant and placebo groups, respectively, 54.7% and 41.0% of participants reported adverse events and 0.8% and 0.4% reported serious adverse events during the double-blind treatment phase. No signal of drug-induced liver injury due to rimegepant was identified. CONCLUSION: Rimegepant 75 mg every other day demonstrated efficacy superior to that of placebo for the preventive treatment of migraine, with a favorable safety profile. NCT05399485. PLAIN LANGUAGE SUMMARY: This study tested the effectiveness of rimegepant for migraine prevention in Japan. Results showed that rimegepant was more effective than placebo in reducing monthly migraine days, with very few adverse effects. These results support the previous findings from a clinical study conducted in the United States and broaden them to a wider population.

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OBJECTIVE: The objectives of this study were to compare the efficacy, including dose response, and safety of rimegepant, an orally administered small-molecule calcitonin gene-related peptide receptor antagonist, with placebo for the acute treatment of migraine in Japan. BACKGROUND: There is a substantial unmet need for the acute treatment of migraine in Japan due to undesirable attributes of existing acute treatments. METHODS: In this Phase 2/3, double-blind, randomized trial, adults with a ≥1-year history of migraine were recruited to 50 study centers in Japan. Participants were randomly assigned to receive rimegepant 25 mg, rimegepant 75 mg, or placebo and instructed to treat a single migraine attack of moderate or severe pain intensity. The randomization was stratified by preventive migraine medication use (yes or no). The primary endpoint was the proportion of participants with pain freedom at 2 h post-dose. Formal hypothesis testing was conducted for rimegepant 75 mg versus placebo. Safety was assessed based on adverse events (AEs). RESULTS: The study was conducted from August 9, 2022, through January 19, 2024. A total of 706 treated participants were evaluable for efficacy (rimegepant 25 mg, n = 238; rimegepant 75 mg, n = 238; placebo, n = 230) and safety (rimegepant 25 mg, n = 239; rimegepant 75 mg, n = 238; placebo, n = 229). Response rates for pain freedom at 2 h post-dose were 21.0% (rimegepant 25 mg), 32.4% (rimegepant 75 mg), and 13.0% (placebo): percentage difference rimegepant 75 mg versus placebo was 19.4% (95% confidence interval 12.0-26.8%, p < 0.001). On-treatment AEs were reported by 7.1% (rimegepant 25 mg), 9.2% (rimegepant 75 mg), and 6.6% (placebo) of treated participants; all were mild or moderate in intensity and most were not considered related to the study drug. CONCLUSION: Rimegepant 75 mg demonstrated efficacy superior to placebo for the acute treatment of migraine, with a favorable safety profile, in participants in Japan. A dose-response relationship was observed for rimegepant (NCT05399459). PLAIN LANGUAGE SUMMARY: This randomized trial was designed to test the effectiveness and safety of rimegepant for the acute treatment of migraine among adults in Japan. Results indicated that rimegepant was more effective than placebo, and the 75 mg dose was observed to be more effective than the 25 mg dose. These results are similar to previous findings from clinical studies in other countries, and suggest that rimegepant can help patients with migraine in Japan.

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Aim This study aimed to evaluate the efficacy and tolerability of rimegepant for the prevention of episodic migraine in participants with a documented history of inadequate response to 2–4 categories of traditional oral preventive medication (OPM). Methods This multinational phase 4 trial consisted of an untreated 28-day observational phase (OP) and a 12-week double-blind treatment (DBT) phase. Participants with 4–14 monthly migraine days (MMDs), &lt;15 monthly headache days (&lt;7 non-migraine) and documented previous inadequate response to 2–4 traditional OPM categories were enrolled. Participants were randomized to rimegepant 75 mg orally disintegrating tablet (ODT) or placebo every other day (EOD). The primary endpoint was mean change from the OP in MMDs through the 12-week DBT phase. Key secondary endpoints were tested hierarchically to control type I errors. Tolerance and safety were assessed throughout the DBT phase. Results In total, 328 participants received rimegepant and 324 received placebo. The most common OPM categories with prior inadequate response were anticonvulsants (61%), beta-blockers (56%) and amitriptyline (51%). The mean ± SD number of MMDs in the OP was 8.4 ± 2.4 and 8.3 ± 2.3, respectively, in the rimegepant (n = 324) and placebo (n = 319) groups. Across the DBT phase, participants who received rimegepant had a significantly larger mean change from the OP in MMDs than those who received placebo (−2.1 vs. −0.5 days; difference = −1.6 days; 95% confidence interval (CI) = −2.1 to −1.2; p &lt; 0.0001). All key secondary endpoints favored rimegepant: (i) percentage of participants with ≥50% reduction from the OP in MMDs with moderate or severe pain intensity across the DBT phase (difference: 20.1%; 95% CI = 13.7 to 26.5; p &lt; 0.0001); (ii) mean change from the OP in MMDs in the first month of the DBT phase (difference: −1.7 days; 95% CI = −2.3 to −1.2; p &lt; 0.0001); (iii) mean change from the OP in MMDs in the last month of the DBT phase (difference: −1.4 days; 95% CI = −2.1 to −0.8; p &lt; 0.0001); (iv) mean change from baseline in Migraine-Specific Quality-of-Life Questionnaire v2.1 Restrictive Role Function domain score at week 12 of the DBT phase (difference: 6.6 points; 95% CI = 3.6 to 9.5; p &lt; 0.0001); and (v) mean change from baseline in Migraine Interictal Burden Scale score at week 12 of the DBT phase (difference: −0.9 points; 95% CI = −1.4 to −0.4; p = 0.0006). Rimegepant was well tolerated with a safety profile not notably different from placebo. Conclusions Rimegepant 75 mg ODT EOD is efficacious and well tolerated for the prevention of episodic migraine in participants with a documented history of inadequate response to 2–4 categories of traditional OPM. Trial Registration ClinicalTrials.gov, NCT05518123 ( https://clinicaltrials.gov/study/NCT05518123 ).

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Menstrually-related migraine (MRM) affects approximately 31–52% of women with migraine and are characterized by increased frequency, severity, and reduced response to conventional therapy during the perimenstrual window. Traditional short-term prevention with non-steroidal anti-inflammatory drugs (NSAIDs) or triptans often fails due to intolerance or contraindications. Rimegepant, a calcitonin gene-related peptide (CGRP) receptor antagonist with indication for both acute and preventive therapy, may offer a novel short-term prophylactic option for perimenstrual migraine. This hypothesis-generating case series includes five women, aged 22–42 years, with episodic migraine and regular menstrual cycles, who received rimegepant 75 mg orally disintegrating tablet every other day, initiated two days prior menstruation and continued until two days post-menstruation. Patients recorded daily headache diaries, and key outcomes included reduction of perimenstrual migraine days, overall migraine frequency, tolerability, and adverse events. Follow-up was conducted after 3–4 cycles. Rimegepant prevented perimenstrual attacks in 17/20 cycles (85%) with no treatment-related adverse events in this small cohort. However, sustained monthly migraine day reduction occurred in only one patient (20%). Three patients (60%) experienced delayed migraine onset 3–7 days post-menstruation, suggesting “temporal displacement” rather than complete prevention. All patients reported high satisfaction with perimenstrual symptom control. Short-term rimegepant was well tolerated and prevented anticipated perimenstrual migraine attacks in most cases. The observed temporal displacement of migraine supports complex hormonal and CGRP-independent mechanisms in menstrual migraine. Randomized controlled trials are warranted to optimize treatment protocols and confirm these preliminary findings.

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The aim of the current analyses of a phase 3 randomized controlled trial conducted in Japan was to assess the long-term safety and effectiveness of rimegepant 75 mg, taken for up to 52 weeks, for the preventive treatment of migraine. The study included adults in Japan with a history of 4–18 migraine attacks/month of moderate or severe pain intensity. After 12 weeks’ double-blind treatment with rimegepant 75 mg or placebo every other day, participants took open-label rimegepant 75 mg every other day and additionally as needed on nonscheduled dosing days (maximum one dose of rimegepant 75 mg per calendar day), for up to 40 weeks. Safety assessments included adverse events and hepatic function. Effectiveness endpoints included change in monthly migraine days, medication use, and changes in migraine-related quality of life and disability. Of 496 participants who received double-blind treatment, 458 participants were treated with rimegepant in the open-label-extension phase (mean age 43.9 years, 90.8% female) for a mean of 37.5 weeks. During the open-label extension phase, the most common adverse events were nasopharyngitis (25.1%) and COVID-19 (13.1%); the rate of adverse events leading to rimegepant discontinuation was 1.3% and the rate of serious adverse events was 0.9%. Aminotransferases >3x the upper limit of normal occurred in four (0.9%) participants during the open-label extension phase; none of these participants had concurrent elevations with total bilirubin >2x upper limit of normal. For the open-label extension phase overall, monthly migraine days of any pain intensity reduced by a mean (95% confidence interval [95% CI]) of –4.5 (95% CI –4.8, –4.2) days with 55.4% (95% CI 50.8, 59.9) of participants experiencing ≥50% reductions compared with the observation period. The use of acute treatments for migraine was low through the open-label extension phase. Improvements from baseline in Migraine-Specific Quality-of-Life Questionnaire v2.1, Migraine Disability Assessment (MIDAS), and EQ visual analog scale were observed through the 52-week study. Sustained effectiveness, with a favorable safety profile, was observed in treatment with rimegepant 75 mg taken up to once daily for up to 52 weeks. Trial registration Clinicaltrials.gov, NCT05399485. Registered May 27, 2022

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Background Comparative evaluations of preventive migraine treatments can help inform clinical decision making for managing migraine in clinical practice. Methods An anchored matching-adjusted indirect comparison analysis was conducted using pooled participant-level data from two phase 3 atogepant trials (ADVANCE and PROGRESS) and one phase 2/3 rimegepant trial (BHV3000-305) to evaluate the relative efficacy and safety/tolerability of atogepant and rimegepant as preventive migraine treatments. Participants receiving atogepant 60 mg once daily, rimegepant orally disintegrating tablet 75 mg once every other day, and placebo were included. Only participants meeting the BHV3000-305 inclusion/exclusion criteria were analyzed: ≥6 monthly migraine days and ≤18 monthly headache days at baseline. The primary efficacy assessment of interest was change in monthly migraine days across weeks 1–12. Results There were 252 participants in the atogepant group and 348 in the rimegepant group. Across weeks 1–12, atogepant 60 mg demonstrated a significantly greater reduction in mean monthly migraine days compared with rimegepant 75 mg (mean difference [95% CI]: −1.65 [−2.49, −0.81]; p &lt; 0.001). Both atogepant and rimegepant demonstrated similar safety/tolerability profiles. Conclusion In this matching-adjusted indirect comparison analysis, oral atogepant 60 mg once daily demonstrated a significantly greater reduction in monthly migraine days compared with rimegepant 75 mg orally disintegrating tablet once every other day.

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