A randomized open-label study to evaluate the effectiveness and safety of once-daily rimegepant 75 mg orally disintegrating tablet for the short-term preventive treatment of fasting-triggered headache in individuals with migraine

Aim To evaluate rimegepant, a calcitonin gene-related peptide receptor antagonist, for short-term prevention of fasting-triggered headache during Ramadan. Methods Participants, aged 18–65 years and diagnosed with migraine or headache attributed to fasting, were randomized to open-label once-daily (QD) rimegepant 75 mg orally disintegrating tablet (ODT) from weeks 1–4 of the fast (Immediate Start arm; n = 52) or weeks 2–4 of the fast (Staggered Start arm; n = 53). The primary endpoint was the difference in number of headache days of any intensity between the Immediate Start and Staggered Start arms during week 1. Other endpoints included headache days during weeks 2–4, moderate-to-severe headache days during weeks 1–4, headache duration (any intensity and moderate-to-severe) during weeks 1–4, rescue medication use during weeks 1–4 and treatment satisfaction. Treatment comparisons utilized nominal p values. Safety endpoints included adverse events (AEs), serious AEs and discontinuations due to AEs. Results All participants (n = 105) had a diagnosis of migraine and a history of headaches during fasting. The number of headache days of any intensity during week 1 (primary endpoint) was lower in the Immediate Start arm vs. the Staggered Start arm (LS mean (95% confidence interval) = 1.74 (1.16–2.31) days vs. 2.92 (2.34–3.49) days; p = 0.005). There were no significant differences between arms during weeks 2–4. Total duration of headaches of any intensity was shorter in the Immediate Start arm vs. the Staggered Start arm during week 1 (LS mean (95% confidence interval) = 10.1 (5.9–17.5) hours vs. 20.0 (13.0–28.3) hours; p = 0.041) and week 4 (LS mean (95% confidence interval) = 0.9 (0.2–3.7) hours vs. 4.6 (2.2–15.5) hours; p = 0.035). The number and duration of moderate-to-severe headaches was significantly ( p < 0.05) lower in the Immediate Start arm vs. the Staggered Start arm during week 1. For the overall 4-week study period, there was a significant reduction in moderate-to-severe headache days per week in the Immediate Start arm vs. the Staggered Start arm (LS mean (95% confidence interval) = 0.60 (0.34–0.86) days vs. 1.00 (0.75–1.26) days; p = 0.038) and a trend towards reduction in headache days per week of any severity (LS mean (95% confidence interval) = 1.05 (0.72–1.39) days vs. 1.50 (1.17–1.84) days; p = 0.070). Use of rescue medication trended lower in the Immediate Start arm vs. the Staggered Start arm at all study weeks; all p > 0.05. Most participants (82.4%) reported being satisfied, very satisfied, or extremely satisfied with rimegepant at end of treatment. No AEs were reported. Conclusions QD rimegepant 75 mg ODT may be effective and well tolerated for short-term prevention of fasting-triggered headache in individuals with migraine.