Safety, tolerability, and pharmacokinetics of single and multiple ascending doses of zavegepant nasal spray in healthy adults from two phase 1 randomized, placebo-controlled trials
Abstract
OBJECTIVE: This study aimed to evaluate the safety and tolerability, and characterize the pharmacokinetic profile, of zavegepant nasal spray in two phase 1 studies.
BACKGROUND: Zavegepant is a high-affinity, selective, small-molecule calcitonin gene-related peptide receptor antagonist, approved as a nasal spray for the acute treatment of migraine in adults.
METHODS: Two single-site, phase 1, placebo-controlled, randomized, double-blind studies evaluated the safety, tolerability, and pharmacokinetic profile of single ascending doses (SAD) and multiple ascending doses (MAD) of zavegepant nasal spray in healthy adults. The SAD study was conducted from October 18, 2018, to March 15, 2019, and the MAD study from September 2, 2019, to December 14, 2019. Zavegepant SAD were 0.1-20 mg single sprays and 40 mg as two 20-mg sprays. Zavegepant MAD 5-20 mg single sprays once daily (QD) and three 40-mg QD regimens given as two 20-mg sprays were evaluated.
RESULTS: In the SAD study, 72 participants were dosed in nine cohorts, and all participants completed the study. In the MAD study, 72 participants were dosed in six cohorts and 71 (99%) completed the study. In each study, zavegepant was rapidly absorbed, with a median time of maximum observed plasma concentration (Tmax) of 0.54 h after a single 10 mg spray (SAD study). Exposure increased with dose, with no evidence of accumulation after repeated QD dosing. In the SAD study, 14 (26%) zavegepant-treated and three (17%) placebo-treated…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 72 participants or records.
Read the paper
Related studies
- Calcium Ions in the Physiology and Pathology of the Central Nervous System
- AI-powered in silico twins: redefining precision medicine through simulation, personalization, and predictive healthcare
- In silico functional, structural and pathogenicity analysis of missense single nucleotide polymorphisms in human MCM6 gene
- In Silico drug repurposing pipeline using deep learning and structure based approaches in epilepsy
- Targeting serotonin receptors with phytochemicals – an in-silico study
- In silico exploration of anti-prostate cancer compounds from differential expressed genes
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.