Safety, tolerability, and efficacy of zavegepant 10 mg nasal spray for the acute treatment of migraine in the USA: a phase 3, double-blind, randomised, placebo-controlled multicentre trial.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Biohaven Pharmaceuticals.

Temporary tattoos to simulate skin disease: report and validation of a novel teaching tool.

PURPOSE: Dermatology is a visual specialty requiring examination and description of skin lesions and the development of analytic skills to establish a diagnosis. Student education in dermatology is challenged by several factors. Although 10% to 15% of a general practitioner's consultations are related to the skin, dermatology is often underrepresented in undergraduate medical curriculums. In addition, more serious lesions, such as malignant melanoma (MM), are promptly biopsied and may not be available for students' examination. The authors carried out this study to learn whether a novel educational tool, a temporary tattoo, could successfully simulate an MM. METHOD: Eighty-one dermatologists and 14 dermatology residents participated in this validity study of a tattoo applied to the arm of a standardized patient (SP) to simulate an MM. The study was conducted at the 82nd Annual Canadian Dermatology Association Conference held in June 2007 in Toronto, Canada. RESULTS: A correct diagnosis was made by 93.8% (76/81) of the dermatologists and 90.5% of the participants (86/95) overall. The tattoo was also evaluated as being very realistic on a five-point Likert scale. CONCLUSIONS: The validation of the tattoo shows potential for use in medical education, such as SP visits and examinations. This teaching tool can be used to simulate a variety of skin lesions, providing a way to visually examine a lesion on the skin of an SP, which would enhance the medical student's learning experience.