PI-110 - A PHASE 1, MULTICENTER, OPEN-LABEL STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF A SINGLE DOSE OF RIMEGEPANT IN CHILDREN (>=6 TO <12 YEARS OF AGE) WITH A HISTORY OF MIGRAINE

C. Lim¹, G. Mo², R. Bhardwaj³, C. Comisar³, B. Emerson², K. Matschke⁴, O. Fisniku⁵, R. Bertz⁶, R. Croop⁶, J. Liu⁷; ¹Pfizer Inc, Cambridge, MA, United States, ²Pfizer Inc, New York, NY, United States, ³Certara USA, Radnor, PA, United States, ⁴Pfizer, Inc., Collegeville, PA, United States, ⁵Pfizer Inc, Lake Forest, IL, United States, ⁶Biohaven Pharmaceuticals, New Haven, CT, United States, ⁷Pfizer Inc, Groton, CT, United States.

Background: Rimegepant 75 mg orally disintegrating tablet (NURTEC® ODT, Pfizer, New York, NY) is approved for acute and preventive treatment of migraine in adults. This Phase 1, open-label study evaluated the safety, tolerability, and pharmacokinetics (PK) of rimegepant in children (≥6 to < 12 years) with a history of migraine.

Methods: A single dose of rimegepant ODT was administered based on body weight. Children ≥15 kg to ≤30 kg received 25 mg (Group 1), children >30 kg to ≤50 kg received 50 mg (2 × 25 mg; Group 2), and children >50 kg received 75 mg (Group 3). Blood samples were collected pre-dose and 0.5, 1.25, 3.5, and 18 hours post-dose. Rimegepant PK parameters including area under the plasma concentration-time curve from time zero to infinity (AUCinf), area under the plasma concentration-time profile from time zero to 24 hours after dosing (AUC24), maximum plasma concentration (Cmax), and time to Cmax (Tmax) were estimated using a population PK approach. A safety follow-up phone call was conducted 4 days after dosing.

Results: All 21 participants treated were analyzed for safety (Group 1 n=7, Group 2 n=9, Group 3 n=5). Twenty participants had ≥1 post dose PK sample and were included in PK analyses. Participants were mostly White (66.7%), female (57.1%), and had a median (range) age of 9.0 (6, 11) years.

Three participants (all in Group 3) had ≥1 adverse event; dizziness (n=1), headache and upper abdominal pain (n=1), and vessel puncture site hematoma (n=1). All AEs were mild and only dizziness was considered treatment-related. No clinically relevant findings regarding laboratory tests, vital signs, ECGs, physical examinations, local tolerability assessments, or the Sheehan-Suicidality Tracking Scale were observed.

Geometric mean estimates of Cmax and AUCinf ranged from 615.9 to 811.1 ng/mL and 1987.8 to 4244.9 ng*h/mL, respectively, across weight groups (Table). Exposures were lowest in Group 1. Median Tmax was 1 to 1.5 hours across weight groups.

Conclusion: A single dose of rimegepant 25–75 mg ODT demonstrated a favorable safety profile in children (≥6 to < 12 years of age) with a history of migraine. Geometric mean estimates of Cmax and AUCinf ranged from 615.9 to 811.1 ng/mL and 1987.8 to 4244.9 ng*h/mL, respectively, across body weight groups. Rimegepant pediatric dose selection will be further evaluated in future studies.