Exposure Matching Using Population Pharmacokinetic Modeling and Simulation to Support Rimegepant Dose Selection for...

Rimegepant is a small molecule calcitonin gene-related peptide receptor antagonist approved as a 75 mg orally disintegrating tablet for the acute treatment of migraine and the prevention of episodic migraine in adults. A population pharmacokinetic model for oral rimegepant was previously developed using data from 11 phase I studies in adults. This analysis updated the population pharmacokinetic model with data from one pediatric (20 participants) and two adult (74 participants) studies. The resultant population pharmacokinetic model was used to predict rimegepant exposure following single or every-other-day dosing in a virtual pediatric population generated using United States national growth charts. Exposure with rimegepant 75 mg orally disintegrating tablet was evaluated in simulated participants aged 6 to 17 years (1000 simulations/1-year age group), and exposure with rimegepant 25, 35, 50, and 75 mg was evaluated in simulated participants weighing 9 to 75 kg (1000 simulations/5 kg increment). Rimegepant doses for pediatric patients were selected using predicted pediatric/adult exposure ratios close to 1 and ≤ 2. The recommended single and every-other-day doses of rimegepant orally disintegrating tablet in the pediatric population were 75 mg in adolescents 12 to < 18 years of age and children 6 to < 12 years of age and with a body weight > 40 kg; 50 mg in children 6 to < 12 years of age with a body weight > 25 to ≤ 40 kg; and 35 mg in children 6 to < 12 years of age with a body weight > 15 to ≤ 25 kg. These selected doses will support further evaluation of rimegepant efficacy and safety in pediatric patients with migraine.