title: Effect of fingolimod (FTY720) on cerebral blood flow, platelet function and macular thickness in healthy volunteers.
abstract: OBJECTIVE
  Fingolimod, a sphingosine 1-phosphate receptor modulator, is the first oral disease modifying therapy approved for the treatment of relapsing multiple sclerosis. The aim of this double-blind, placebo-controlled study was to evaluate the effect of fingolimod on cerebral blood flow, platelet function and macular thickness in healthy volunteers.
  
  
  METHODS
  The study included 88 healthy volunteers who received fingolimod 0.5 mg or 1.25 mg or matched placebo over a period of 4 weeks. Transcranial colour coded sonography was performed to measure mean blood flow velocities, the platelet function was measured by the PFA-100® assay using a collagen/epinephrine cartridge and macular thickness was measured using optical coherence tomography. An assessment of non-inferiority of fingolimod vs. placebo was performed against a reference value (20% of the overall baseline value).
  
  
  RESULTS
  All 88 randomized participants completed the study. At day 28 compared with baseline value, for 0.5 mg, 1.25 mg and placebo treatments, the mean middle cerebral artery blood flow velocity decreased by 4, 1 and 3.7 cm s(-1), respectively. The platelet function analyzer closure time increase was not significant (7.8, 7.5 and 10.4 s, respectively). The mean percentage change in the central foveal thickness from baseline for both eyes was below 3% for all groups. The safety profile of fingolimod in this study was found consistent with the previous reports.
  
  
  CONCLUSIONS
  In healthy volunteers, the changes seen with both fingolimod doses were found to be within normal variability, non-inferior and comparable with those observed with placebo for all the pharmacodynamic parameters assessed.
authors: Novartis Pharma AG, Basel, Switzerland.
authors: Magdalena
authors: M
authors: Ocwieja
authors: Karin
authors: K
authors: Meiser
authors: Olivier J
authors: OJ
authors: David
authors: Jessica
authors: J
authors: Valencia
authors: Frank
authors: F
authors: Wagner
authors: Stephan J
authors: SJ
authors: Schreiber
authors: Uwe
authors: U
authors: Pleyer
authors: Sabine
authors: S
authors: Ziemer
authors: Robert
authors: R
authors: Schmouder
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D000068876:Fingolimod Hydrochloride; D006801:Humans; D008266:Macula Lutea / Q000033:anatomy & histology / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D011409:Propylene Glycols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D049349:Receptors, Lysosphingolipid / Q000187:drug effects; D013110:Sphingosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine
keywords: cerebral blood flow; fingolimod; healthy volunteers; macular thickness; platelet function; sphingosine 1-phosphate