PMID- 38366390
OWN - NLM
STAT- MEDLINE
DCOM- 20240219
LR  - 20240228
IS  - 1468-2982 (Electronic)
IS  - 0333-1024 (Linking)
VI  - 44
IP  - 2
DP  - 2024 Feb
TI  - Bioequivalence of rimegepant, a small molecule CGRP receptor antagonist, 
      administered as an oral tablet, a sublingual orally disintegrating tablet, and a 
      supralingual orally disintegrating tablet: two phase 1 randomized studies in 
      healthy adults.
PG  - 3331024231219505
LID - 10.1177/03331024231219505 [doi]
AB  - BACKGROUND: Rimegepant is an orally administered small molecule calcitonin 
      gene-related peptide receptor antagonist indicated for the acute and preventive 
      treatment of migraine. METHODS: Two single-center, phase 1, open-label, 
      randomized bioequivalence studies were conducted in healthy adult non-smokers, 
      aged 18-55 years. One study compared the rate and extent of absorption of the 
      marketed formulation of rimegepant 75 mg orally disintegrating tablet (ODT) 
      administered sublingually with rimegepant 75 mg oral tablet, an earlier 
      development formulation; the second compared the rate and extent of absorption of 
      75 mg rimegepant ODT administered supralingually with rimegepant oral tablet. 
      RESULTS: The ln-transformed geometric mean ratios for the area under the curve 
      (AUC) from time 0 to the last available concentration time point (time t) 
      (AUC(0-t)), AUC from time 0 to infinity (AUC(0-inf)), and maximum observed 
      concentration (C(max)) of sublingual rimegepant ODT vs. rimegepant tablet were 
      97, 97, and 105%, respectively, and the 90% confidence intervals (CIs) were all 
      within the predefined range (80-125%) for bioequivalence. The ln-transformed 
      geometric mean ratios for the AUC(0-t) and AUC(0-inf) of supralingual rimegepant 
      ODT vs. rimegepant tablet were 98%, the 90% CIs were within the predefined range 
      (80-125%), and the geometric mean ratio for C(max) was 103% with the 95% upper 
      confidence bound for the scaled average bioequivalence criterion of -0.0575 
      (within-participant coefficient of variation for the reference for C(max) > 30%) 
      for bioequivalence. CONCLUSIONS: Rimegepant 75 mg ODT, administered sublingually 
      or supralingually, and rimegepant 75 mg oral tablet were bioequivalent.
FAU - Croop, Robert
AU  - Croop R
AD  - Biohaven Pharmaceuticals, New Haven, CT, USA.
FAU - Bhardwaj, Rajinder
AU  - Bhardwaj R
AD  - Certara USA, Princeton, NJ, USA.
FAU - Anderson, Matt S
AU  - Anderson MS
AD  - Certara USA, Princeton, NJ, USA.
FAU - Matschke, Kyle T
AU  - Matschke KT
AD  - Pfizer Inc., New York, NY, USA.
FAU - Hould, Jennifer
AU  - Hould J
AD  - Biohaven Pharmaceuticals, New Haven, CT, USA.
FAU - Bertz, Richard
AU  - Bertz R
AD  - Biohaven Pharmaceuticals, New Haven, CT, USA.
FAU - Liu, Jing
AU  - Liu J
AD  - Pfizer Inc., New York, NY, USA.
FAU - Lipton, Richard B
AU  - Lipton RB
AUID- ORCID: 0000-0003-2652-2897
AD  - Albert Einstein College of Medicine, Bronx, NY, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - England
TA  - Cephalalgia
JT  - Cephalalgia : an international journal of headache
JID - 8200710
RN  - 0 (Calcitonin Gene-Related Peptide Receptor Antagonists)
RN  - 0 (Piperidines)
RN  - 0 (Pyridines)
RN  - 1383NM3Q0H (rimegepant sulfate)
RN  - 0 (Tablets)
SB  - IM
MH  - Adult
MH  - Humans
MH  - Administration, Oral
MH  - Area Under Curve
MH  - *Calcitonin Gene-Related Peptide Receptor Antagonists
MH  - Cross-Over Studies
MH  - *Piperidines
MH  - *Pyridines
MH  - Tablets
MH  - Therapeutic Equivalency
MH  - Adolescent
MH  - Young Adult
MH  - Middle Aged
OTO - NOTNLM
OT  - Bioequivalent
OT  - ODT
OT  - absorption
OT  - formulation
OT  - migraine
COIS- Declaration of conflicting interestsRobert Croop was an employee of Biohaven 
      Pharmaceuticals, owns stock in Biohaven Ltd, was an employee of Pfizer, has 
      received research payments from Pfizer and provides services to Collima LLC, 
      which has had consulting agreements with Pfizer, Aptose Biosciences Inc., 
      Manistee Therapeutics and Vida Ventures Management Co., L.L.C. Jennifer Hould and 
      Richard Bertz are employed by and own stock/stock options in Biohaven 
      Pharmaceuticals. Jing Liu and Kyle T. Matschke are employed by and own 
      stock/stock options in Pfizer Inc. Rajinder Bhardwaj, PhD, and Matt S. Anderson, 
      PhD, are employed by Certara USA, which was a paid consultant of Biohaven 
      Pharmaceuticals. Richard B. Lipton serves on the editorial board of Neurology and 
      as senior advisor to Headache but is not paid for his roles on these journals. He 
      has received research support from the NIH. He also receives support from the 
      National Headache Foundation. He receives research grants from Allergan/Abbvie, 
      Amgen, Dr Reddy's Laboratories and Novartis. He has reviewed for the NIA and 
      NINDS and serves as consultant, advisory board member, or has received honoraria 
      from Allergan/Abbvie, Amgen, Biohaven, Dr Reddy's Laboratories, electroCore, Eli 
      Lilly, GlaxoSmithKline, Merck, Novartis, Teva and Vedanta. He receives royalties 
      from Wolff's Headache (8th edition, Oxford University Press, 2009) and Informa. 
      He holds stock options in Biohaven Pharmaceuticals and Manistee.
EDAT- 2024/02/17 12:44
MHDA- 2024/02/19 06:42
CRDT- 2024/02/17 00:53
PHST- 2024/02/19 06:42 [medline]
PHST- 2024/02/17 12:44 [pubmed]
PHST- 2024/02/17 00:53 [entrez]
AID - 10.1177/03331024231219505 [doi]
PST - ppublish
SO  - Cephalalgia. 2024 Feb;44(2):3331024231219505. doi: 10.1177/03331024231219505.