A phase 1, multicenter, open-label study to evaluate the pharmacokinetics, safety, and tolerability of a single dose of rimegepant in children (aged ≥6 to <12 years) with a history of migraine.

OBJECTIVE

To evaluate pharmacokinetics (PK), safety, and tolerability of a weight-adjusted dose of rimegepant orally disintegrating tablet (ODT) in children (aged ≥6 to <12 years) with a history of migraine.

BACKGROUND

Rimegepant 75 mg ODT is approved for acute treatment of migraine (with or without aura) and preventive treatment of episodic migraine in adults. Studies of rimegepant in pediatric populations have not been conducted to date.

METHODS

In this phase 1 open-label study, a single dose of rimegepant ODT was administered, based on body weight, to children aged ≥6 to <12 years. Children with body weight ≥15 kg to ≤30 kg received 25 mg (group 1; n = 7), children >30 kg to ≤50 kg received 50 mg (2 × 25 mg; group 2; n = 9), and children >50 kg received 75 mg (group 3; n = 5). Blood samples were collected pre-dose and 0.5, 1.25, 3.5, and 18 h post-dose and then analyzed using a validated bioanalytical assay. Rimegepant PK parameters, including area under the plasma concentration-time curve (AUC) from time zero to infinity (AUCinf), AUC from time zero to 24 h after dosing, maximum plasma concentration (Cmax), and time to Cmax were estimated using a population PK approach in which pediatric PK data from this study were used to update a previous rimegepant population PK model developed with adult data. A safety follow-up phone call was conducted 4 days after dosing.

RESULTS

Twenty participants with ≥1 post-dose PK sample were included in PK analyses. All 21 participants treated were analyzed for safety. A majority of the study population was White (67%) and female (57%), had a median (range) age of 9.0 (6 to 11) years, and a mean (standard deviation) body weight of 37.7 (12.3) kg. 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. Rimegepant exposures, particularly AUCinf values, were lower in the two lower-weight groups (groups 1 and 2) than in the higher-weight group (group 3). Median time to Cmax was 1 to 1.5 h across weight/dose groups. Three (14%) participants (all in group 3) had ≥1 adverse event; all were mild in severity. No clinically relevant findings regarding laboratory tests, vital signs, electrocardiograms, physical examinations, local tolerability assessments, or the Sheehan-Suicidality Tracking Scale were observed.

CONCLUSIONS

A single weight-adjusted dose of rimegepant ODT demonstrated a favorable safety profile in children aged ≥6 to <12 years with a history of migraine. Exposures in children >50 kg receiving 75 mg rimegepant were similar to observed exposures in adults receiving 75 mg. However, exposures in children >30 kg to ≤50 kg receiving 50 mg rimegepant and in children ≥15 kg to ≤30 kg receiving 25 mg rimegepant were lower than exposures in adults receiving 75 mg. These findings will be the basis for further refinement of pediatric dose in future studies.