Clinical pharmacokinetic studies with INN 00835 (nemifitide), a novel pentapeptide antidepressant.
Nemifitide (4-fluoro-L-phenylalanyl-trans-4-hydroxy-L-prolyl-L-arginylglycyl-L-tryptophanamide ditrifluoroacetate) is a novel antidepressant, currently in phase 2/3 clinical trials. The purpose of our phase 1 clinical trials (conducted over a three year period) was to provide safety and pharmacokinetic data to support its clinical development as an antidepressant drug. Single and multiple doses ranging from 18 to 320 mg were administered subcutaneously to healthy volunteers in five phase 1 studies. Plasma concentrations of unchanged parent drug were determined by a validated LC/MS/MS method in blood samples collected at timepoints between 10 min and 72 h after dosing. Nemifitide was rapidly absorbed (C(max) at 10 min) and eliminated (t(1/2) 15-30 min) in most subjects. Regression and power model analyses were used to evaluate the data. The results indicate that pharmacokinetic parameters: AUC(0-t), AUC (0-infinity) and C(max), were close to dose proportional in the dose range investigated. There was no evidence of systemic accumulation of drug following 5 daily doses. No serious adverse events or clinically significant systemic adverse events occurred at any of the doses investigated in the over 100 subjects dosed in these studies. Drug-related adverse events were limited to local and transient skin reactions (pain and/or erythema) at the injection site, especially at the high doses administered: 240 and 320 mg.
Feighner
John P
JP
Innapharma, Inc., 1 Maynard Drive, Suite 205, Park Ridge, New Jersey 07656, USA.
Nicolau
Gabriela
G
Abajian
Henry
H
Marricco
Nadia Cardillo
NC
Morrison
John
J
Sverdlov
Lev
L
Hlavka
Joseph
J
Tonelli
George
G
Di Spirito
Carlo
C
Faria
George
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000493:pharmacokinetics*
D000928:Antidepressive Agents; D009842:Oligopeptides; C406668:nemifitide ditriflutate