OBJECTIVE: To report the results of a 24-month extension of a phase II trial assessing the efficacy, safety, and tolerability of the once-daily oral sphingosine-1-phosphate receptor modulator, fingolimod (FTY720), in relapsing multiple sclerosis (MS). METHODS: In the randomized, double-blind, placebo-controlled core study, 281 patients receivedplacebo or FTY720, 1.25 or 5.0 mg/day, for 6 months. During the subsequent dose-blinded extension, patients assigned to placebo were re-randomized to either dose of FTY720; those originally assigned to FTY720 continued at the same dose. Patients receiving FTY720 5.0 mg were switched to 1.25 mg during the month 15 to month 24 study visits. RESULTS: Of 281 patients randomized in the core study, 250 (89%) entered the extension phase, and 189 (75.6%) received treatment for 24 months. During the core study, FTY720 significantly reduced gadolinium-enhanced (Gd(+)) lesions and annualized relapse rate (ARR) compared with placebo, with no differences between doses. During the extension phase, patients who switched from placebo to FTY720 showed clear reductions in ARR and lesion counts compared with the placebo phase; ARR and lesion counts remained low in patients who continued FTY720 treatment. After 24 months, 79 to 91% of patients were free from Gd(+) lesions and up to 77% of patients remained relapse free. FTY720 was well tolerated; no new safety concerns emerged during months 7 to 24 compared with the 6-month core study. CONCLUSIONS: Once-daily oral treatment with FTY720, 1.25 or 5.0 mg, for up to 2 years, was well tolerated and was associated with low relapse rates and lesion activity.
RCT Entities:
OBJECTIVE: To report the results of a 24-month extension of a phase II trial assessing the efficacy, safety, and tolerability of the once-daily oral sphingosine-1-phosphate receptor modulator, fingolimod (FTY720), in relapsing multiple sclerosis (MS). METHODS: In the randomized, double-blind, placebo-controlled core study, 281 patients received placebo or FTY720, 1.25 or 5.0 mg/day, for 6 months. During the subsequent dose-blinded extension, patients assigned to placebo were re-randomized to either dose of FTY720; those originally assigned to FTY720 continued at the same dose. Patients receiving FTY720 5.0 mg were switched to 1.25 mg during the month 15 to month 24 study visits. RESULTS: Of 281 patients randomized in the core study, 250 (89%) entered the extension phase, and 189 (75.6%) received treatment for 24 months. During the core study, FTY720 significantly reduced gadolinium-enhanced (Gd(+)) lesions and annualized relapse rate (ARR) compared with placebo, with no differences between doses. During the extension phase, patients who switched from placebo to FTY720 showed clear reductions in ARR and lesion counts compared with the placebo phase; ARR and lesion counts remained low in patients who continued FTY720 treatment. After 24 months, 79 to 91% of patients were free from Gd(+) lesions and up to 77% of patients remained relapse free. FTY720 was well tolerated; no new safety concerns emerged during months 7 to 24 compared with the 6-month core study. CONCLUSIONS: Once-daily oral treatment with FTY720, 1.25 or 5.0 mg, for up to 2 years, was well tolerated and was associated with low relapse rates and lesion activity.
Authors: Volker Brinkmann; Andreas Billich; Thomas Baumruker; Peter Heining; Robert Schmouder; Gordon Francis; Shreeram Aradhye; Pascale Burtin Journal: Nat Rev Drug Discov Date: 2010-10-29 Impact factor: 84.694
Authors: Laura J Sim-Selley; Paulette B Goforth; Mba U Mba; Timothy L Macdonald; Kevin R Lynch; Sheldon Milstien; Sarah Spiegel; Leslie S Satin; Sandra P Welch; Dana E Selley Journal: J Neurochem Date: 2009-05-31 Impact factor: 5.372
Authors: Niannian Ji; Animesh Somanaboeina; Aakanksha Dixit; Kazuyuki Kawamura; Neil J Hayward; Christopher Self; Gary L Olson; Thomas G Forsthuber Journal: J Immunol Date: 2013-10-11 Impact factor: 5.422
Authors: Barry S Shea; Sarah F Brooks; Benjamin A Fontaine; Jerold Chun; Andrew D Luster; Andrew M Tager Journal: Am J Respir Cell Mol Biol Date: 2010-01-15 Impact factor: 6.914
Authors: Bin Ma; Kevin M Guckian; Edward Yin-Shiang Lin; Wen-Cherng Lee; Daniel Scott; Gnanasambandam Kumaravel; Timothy L Macdonald; Kevin R Lynch; Cheryl Black; Sowmya Chollate; Kyungmin Hahm; Gregg Hetu; Ping Jin; Yi Luo; Ellen Rohde; Anthony Rossomando; Robert Scannevin; Joy Wang; Chunhua Yang Journal: Bioorg Med Chem Lett Date: 2010-02-06 Impact factor: 2.823