Rimegepant, a small molecule calcitonin gene-related peptide receptor antagonist, has shown efficacy in the acute treatment of migraine using a standard tablet formulation. The objective of this ...trial was to compare the efficacy, safety, and tolerability of a novel orally disintegrating tablet formulation of rimegepant at 75 mg with placebo in the acute treatment of migraine.
In this double-blind, randomised, placebo-controlled, multicentre phase 3 trial, adults aged 18 years or older with history of migraine of at least 1 year were recruited to 69 study centres in the USA. Participants were randomly assigned to receive rimegepant (75 mg orally disintegrating tablet) or placebo and instructed to treat a single migraine attack of moderate or severe pain intensity. The randomisation was stratified by the use of prophylactic medication (yes or no), and was carried out using an interactive web response system that was accessed by each clinical site. All participants, investigators, and the sponsor were masked to treatment group assignment. The coprimary endpoints were freedom from pain and freedom from the most bothersome symptom at 2 h postdose. The efficacy analyses used the modified intention-to-treat population, which included all patients who were randomly assigned, had a migraine attack with pain of moderate or severe intensity, took a dose of rimegepant or placebo, and had at least one efficacy assessment after administration of the dose. The safety analyses included all randomly assigned participants who received at least one dose of study medication. This study is registered with ClinicalTrials.gov, number NCT03461757, and is closed to accrual.
Between Feb 27 and Aug 28, 2018, 1811 participants were recruited and assessed for eligibility. 1466 participants were randomly assigned to the rimegepant (n=732) or placebo (n=734) groups, of whom 1375 received treatment with rimegepant (n=682) or placebo (n=693), and 1351 were evaluated for efficacy (rimegepant n=669, placebo n=682). At 2 h postdose, rimegepant orally disintegrating tablet was superior to placebo for freedom from pain (21% vs 11%, p<0·0001; risk difference 10, 95% CI 6–14) and freedom from the most bothersome symptom (35% vs 27%, p=0·0009; risk difference 8, 95% CI 3–13). The most common adverse events were nausea (rimegepant n=11 2%; placebo n=3 <1%) and urinary tract infection (rimegepant n=10 1%; placebo n=4 1%). One participant in each treatment group had a transaminase concentration of more than 3 × the upper limit of normal; neither was related to study medication, and no elevations in bilirubin greater than 2 × the upper limit of normal were reported. Treated participants reported no serious adverse events.
In the acute treatment of migraine, a single 75 mg dose of rimegepant in an orally disintegrating tablet formulation was more effective than placebo. Tolerability was similar to placebo, with no safety concerns.
Biohaven Pharmaceuticals.
Intranasal formulations can provide treatment options for people with migraine in whom oral drugs are ineffective, slow-acting, or intolerable because of nausea and vomiting. Zavegepant, an ...intranasally administered small molecule calcitonin gene-related peptide (CGRP) receptor antagonist, was previously assessed in a phase 2/3 trial. This phase 3 trial aimed to compare the efficacy, tolerability, safety, and timecourse of response for zavegepant nasal spray with placebo in the acute treatment of migraine.
This double-blind, randomised, placebo-controlled, multicentre phase 3 trial, conducted at 90 academic medical centres, headache clinics, and independent research facilities in the USA, recruited adults (aged ≥18 years) with a history of two to eight moderate or severe migraine attacks per month. Participants were randomly assigned (1:1) to zavegepant 10 mg nasal spray or matching placebo and self-treated a single migraine attack of moderate or severe pain intensity. Randomisation was stratified by the use or non-use of preventive medication. Study centre personnel entered eligible participants into the study using an interactive web response system that was operated and managed by an independent contract research organisation. All participants, investigators, and the funder were masked to group assignment. The coprimary endpoints, freedom from pain and freedom from the most bothersome symptom at 2 h after the treatment dose, were assessed in all randomly assigned participants who took the study medication, had a migraine attack of moderate or severe pain intensity at baseline, and provided at least one evaluable post-baseline efficacy datapoint. Safety was analysed in all randomly assigned participants who received at least one dose. The study is registered with ClinicalTrials.gov, number NCT04571060, and is closed to accrual.
Between Oct 27, 2020, and Aug 20, 2021, 1978 participants were recruited and assessed for eligibility. 1405 participants were eligible (703 were assigned to zavegepant and 702 to placebo), and 1269 were included in the efficacy analysis set (623 in the zavegepant group and 646 in the placebo group). 2 h after the treatment dose, more participants in the zavegepant group than in the placebo group had pain freedom (147 24% of 623 participants vs 96 15% of 646 participants, risk difference 8·8 percentage points, 95% CI 4·5–13·1; p<0·0001) and freedom from their most bothersome symptom (247 40% vs 201 31%, risk difference 8·7 percentage points, 3·4–13·9; p=0·0012). The most common adverse events in either treatment group (≥2%) were dysgeusia (129 21% of 629 in the zavegepant group vs 31 5% of 653 in the placebo group), nasal discomfort (23 4% vs five 1%), and nausea (20 3% vs seven 1%). No signal of hepatotoxicity due to zavegepant was identified.
Zavegepant 10 mg nasal spray was efficacious in the acute treatment of migraine, with favourable tolerability and safety profiles. Additional trials are needed to establish the long-term safety and consistency of effect across attacks.
Biohaven Pharmaceuticals.
The eighteen original interdisciplinary essays in Lux in Tenebris explore the alchemical, magical, kabbalistic, rosicrucian and theosophical verbal and visual symbolism in the history of Western ...Esotericism, from the middle ages to the present day.
This essay examines the elaborate title pages of some of alchemist, astrologer, and bibliophile John Dee's publications with a focus on the two best known works that feature his famous Hieroglyphic ...Monad, the Propaedeumata Aphoristica (1558) and Monas Hieroglyphica (1564). The aim is to cast light on its context, identify sources for some textual influences in the works, unpack the visual symbolism in the two "monadic" title pages in relation to the two complementary sciences of "superior" and "inferior" astronomy, speculate on some of the more enigmatic details, and conclude with a brief discussion of a possible astrological significance to the dates of composition of the Monas Hieroglyphica.
This essay investigates the relationships between early modern alchemy and the Jewish mystical tradition of Kabbalah, following its introduction to the Christian West by Giovanni Pico della Mirandola ...at the end of the fifteenth century, and its promulgation by Johannes Reuchlin in the early sixteenth century. New exponents of Christian Cabala were excited by the exegetical methods of Kabbalah, and some alchemists, seeking fresh ways of interpreting enigmatic alchemical texts and the Book of Nature, experimented with novel combinations of the two practices in the hope of gaining insights into their work. While many of these figures were engaged in the broader concerns of Paracelsian philosophy, those experimenting with combinations of alchemy and Cabala nevertheless spanned the spectrum from metallic transmutation to chemical medicine. While focusing on the investigation of kabbalistic elements in alchemical texts produced by Christian authors, rather than the discussion of alchemical material in Jewish Kabbalistic sources, I also briefly consider one apparently authentic Jewish combination of alchemy and Kabbalah: the Aesch Mezareph, published by Christian Knorr von Rosenroth in the Kabbala Denudata.
Few fields of academic research are surrounded by so many misunderstandings and misconceptions as the study of Western esotericism. For twenty years now, the Centre for History of Hermetic Philosophy ...and Related Currents (University of Amsterdam) has been at the forefront of international scholarship in this domain. This anniversary volume seeks to make the modern study of Western esotericism known beyond specialist circles, while addressing a range of misconceptions, biases, and prejudices that still tend to surround it. Thirty major scholars in the field respond to questions about a wide range of unfamiliar ideas, traditions, practices, problems, and personalities that are central to this area of research. By challenging many taken-for-granted assumptions about religion, science, philosophy, and the arts, this volume demonstrates why the academic study of esotericism leads us to reconsider much that we thought we knew about the story of Western culture.
Lux in Tenebris is a collection of eighteen original interdisciplinary essays that address aspects of the verbal and visual symbolism in the works of significant figures in the history of Western ...Esotericism, covering such themes as alchemy, magic, kabbalah, angels, occult philosophy, Platonism, Rosicrucianism, and Theosophy. Part I: Middle Ages & Early Modernity ranges from Gikatilla, Ficino, Camillo, Agrippa, Weigel, Bohme, Yvon, and Swedenborg, to celestial divination in Russia. Part II: Modernity & Postmodernity moves from occultist thinkers Schwaller de Lubicz and Evola to esotericism in literature, art, and cinema, in the works of Colquhoun, Degouve de Nuncques, Bruskin, Doitschinoff, and Perez-Reverte, with an essay on esoteric theories of colour. Contributors are: Michael J.B. Allen, Susanna Akerman, Lina Bolzoni, Aaron Cheak, Robert Collis, Francesca M. Crasta, Per Faxneld, Laura Follesa, Victoria Ferentinou, Joshua Gentzke, Joscelyn Godwin, Hans Thomas Hakl, Theodor Harmsen, Elke Morlok, Noel Putnik, Jonathan Schorsch, Gyorgy Szonyi, Carsten Wilke, and Thomas Willard.
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