FTY720: placebo-controlled study of the effect on cardiac rate and rhythm in healthy subjects.
The purpose of this double-blind, placebo-controlled study was to measure the effects of FTY720, a novel immunomodulator, on heart rate and rhythm in healthy volunteers. Subjects (n = 66) were randomized to FTY720 1.25 mg or 5 mg or placebo administered once daily for 7 days. Continuous telemetry revealed an acute, dose-dependent decrease in mean heart rate (10-bpm decrease vs placebo) following the first dose of FTY720, with a nadir generally 4 hours postdose. Although a persistent FTY720-related decrease in heart rate was measured from day 2 to day 7, additional doses of FTY720 after day 2 resulted in no further incremental decreases. Mean PR interval increased by approximately 8 to 10 msec in FTY720-treated subjects on day 1. FTY720 did not increase the QRS or QT interval. These results confirm that the first dose of FTY720 has a mild to moderate negative chronotropic effect.
Schmouder
Robert
R
Exploratory Development, Novartis Pharmaceutical Corporation, East Hanover, New Jersey, USA.
Serra
Denise
D
Wang
Yibin
Y
Kovarik
John M
JM
DiMarco
John
J
Hunt
Thomas L
TL
Bastien
Marie-Claude
MC
D000293:Adolescent; D000328:Adult; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015716:Electrocardiography, Ambulatory / Q000187:drug effects; D005080:Exercise Test; D005260:Female; D000068876:Fingolimod Hydrochloride; D006329:Heart Conduction System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D011409:Propylene Glycols / Q000009:adverse effects / Q000494:pharmacology*; D012016:Reference Values; D013110:Sphingosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine