PII-194 - A PHASE 1 STUDY COMPARING PHARMACOKINETICS OF RIMEGEPANT 25 MG ORALLY DISINTEGRATING TABLET (ODT) PEDIATRIC FORMULATION WITH RIMEGEPANT 75 MG ODT ADULT FORMULATION, WHEN ADMINISTERED AT A SINGLE DOSE OF 75 MG UNDER FASTING CONDITIONS

G. Mo¹, R. Bhardwaj², K. Matschke³, J. Madonia⁴, D. Ding¹, C. Huntington¹, B. Emerson¹, R. Croop⁴, R. Bertz⁴, J. Liu¹; ¹Pfizer, Inc., ²Certara USA, ³Pfizer, Inc., Collegeville, PA, USA, ⁴Biohaven Pharmaceuticals.

Background: Rimegepant orally disintegrating tablet (NURTEC® ODT, Pfizer, New York, NY) is a calcitonin gene-related peptide receptor antagonist indicated for acute treatment of migraine with or without aura and for preventive treatment of episodic migraine in adults. The recommended dose is 75 mg. This study compared the rate and extent of absorption of a pediatric rimegepant 25 mg ODT formulation when administered at a dose of 75 mg (i.e., 3 x 25 mg) with the adult rimegepant 75 mg ODT (i.e., 1 x 75 mg) formulation.

Methods: This was a single center, Phase 1, randomized, open-label, single-dose, 2-treatment, 4-period, 2-sequence, replicated crossover study in healthy adults. Treatment sequence 1 was: Period 1 = 3 x 25 mg, Period 2 = 1 x 75 mg, Period 3 = 3 x 25 mg, Period 4 = 1 x 75 mg. Treatment sequence 2 was: Period 1 = 1 x 75 mg, Period 2 = 3 x 25 mg, Period 3 = 1 x 75 mg, Period 4 = 3 x 25 mg. Participants received rimegepant under fasting condition in each period, followed by 72 hours of pharmacokinetic (PK) assessments. There was a washout period of ≥ 7 days between doses. The primary PK endpoints were AUCinf, AUClast, and Cmax. Parameters were analyzed according to US-Food and Drug Administration (FDA), European Medicines Agency (EMA), and Canadian Health Products and Food Branch (HPFB) guidance.

Results: Comparison of pediatric rimegepant 3 × 25 mg ODT and adult rimegepant 1 × 75 mg ODT determined the ratio adjusted geometric mean of AUClast to be between 101.34% – 101.41%, of AUCinf to be between 100.56% – 100.62%, and of Cmax to be between 101.05% – 101.51%, depending on the statistical model (see Table for FDA model results). The 90% confidence intervals of the ratios of the PK parameters all contained 100%, indicating no statistically significant difference between the 2 treatments. Additionally, bioequivalence criteria were met for all parameters under FDA, EMA, and HPFB guidance.

Conclusion: Pediatric rimegepant 3 × 25 mg ODT is bioequivalent to adult rimegepant 1 × 75 mg ODT under fasting condition in healthy participants.