Pharmacokinetics, Safety, and Tolerability of Fevipiprant (QAW039), a Novel CRTh2 Receptor Antagonist: Results From 2 Randomized, Phase 1, Placebo-Controlled Studies in Healthy Volunteers.
We evaluated the pharmacokinetics (PK), safety, and tolerability of a novel oral CRTh2 antagonist, fevipiprant (QAW039), in healthy subjects. Peak concentrations of fevipiprant in plasma were observed 1-3 hours postdosing. Concentrations declined in a multiexponential manner, followed by an apparent terminal phase (t1/2 , ∼20 hours). Steady state was achieved in 4 days with <2-fold accumulation. Elimination was partly by renal excretion (≤30% of the dose) and glucuronidation. Food had minimal impact on the PK of fevipiprant, and it was well tolerated at single and multiple oral doses up to 500 mg/day. No dose-dependent adverse events were observed, and all the events were mild or moderate in severity. Systemic concentrations were sufficiently high to achieve relevant target occupancy, considering in vitro pharmacology data. In summary, the data support further development as a once-daily oral therapy for allergic diseases.
Novartis Pharma AG, Basel, Switzerland.
Veit J
VJ
Erpenbeck
SGS-Life Sciences, Antwerp, Belgium.
Eva
E
Vets
SGS-Life Sciences, Antwerp, Belgium.
Lien
L
Gheyle
Novartis Institutes for Biomedical Research, Horsham, United Kingdom.
Wande
W
Osuntokun
Novartis Pharma AG, Basel, Switzerland.
Michael
M
Larbig
Novartis Healthcare Private Limited, Hyderabad, India.
Srikanth
S
Neelakantham
Novartis Institutes for Biomedical Research, Cambridge, MA, USA.
David
D
Sandham
Novartis Institutes for Biomedical Research, Horsham, United Kingdom.
Gerald
G
Dubois
Novartis Pharma AG, Basel, Switzerland.
Walid
W
Elbast
Novartis Institutes for Biomedical Research, Horsham, United Kingdom.
Paul
P
Goldsmith
Novartis Pharma AG, Basel, Switzerland.
Markus
M
Weiss
D000284:Administration, Oral; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D018565:Food-Drug Interactions; D006207:Half-Life; D006801:Humans; D007210:Indoleacetic Acids / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*
D007210:Indoleacetic Acids; D011725:Pyridines; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C000604875:fevipiprant; C036293:prostaglandin D2 receptor
QAW039; fevipiprant; healthy subjects; pharmacokinetics; safety