title: Pharmacological effects of CS-0777, a selective sphingosine 1-phosphate receptor-1 modulator: results from a 12-week, open-label pilot study in multiple sclerosis patients.
abstract: CS-0777 is a selective sphingosine 1-phosphate receptor-1 modulator under investigation for treatment of multiple sclerosis (MS). We conducted an open-label, pilot study in 25 MS patients to assess the safety, pharmacokinetics, pharmacodynamics and exploratory efficacy of oral CS-0777 (0.1, 0.3 and 0.6 mg), administered once weekly or every other week for 12 weeks. CS-0777 resulted in a pronounced, dose-dependent decrease in lymphocytes and CD4 T cell subsets, which returned to baseline within 4 weeks after the last dose. Overall, CS-0777 was safe and well-tolerated. These results require confirmation in a double-blind, placebo-controlled and adequately powered phase 2 study in MS.
authors.affiliation: Daiichi Sankyo Pharma Development, 399 Thornall Street, Edison, New Jersey 08837, USA. jim.moberly@grunenthal.com
authors.forename: James B
authors.initials: JB
authors.lastname: Moberly
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Ford
authors.forename: Hamim
authors.initials: H
authors.lastname: Zahir
authors.forename: Shuquan
authors.initials: S
authors.lastname: Chen
authors.forename: Takashi
authors.initials: T
authors.lastname: Mochizuki
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Truitt
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Vollmer
mesh_terms: D000284:Administration, Oral; D000605:Amino Alcohols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008231:Lymphopenia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008246:Lysophospholipids / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D010865:Pilot Projects; D011758:Pyrroles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D000605:Amino Alcohols; C569297:CS 0777; D008246:Lysophospholipids; D011758:Pyrroles; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D013110:Sphingosine