PMID- 24659797
OWN - NLM
STAT- MEDLINE
DCOM- 20150126
LR  - 20211021
IS  - 1468-330X (Electronic)
IS  - 0022-3050 (Print)
IS  - 0022-3050 (Linking)
VI  - 85
IP  - 11
DP  - 2014 Nov
TI  - Oral ponesimod in relapsing-remitting multiple sclerosis: a randomised phase II 
      trial.
PG  - 1198-208
LID - 10.1136/jnnp-2013-307282 [doi]
AB  - OBJECTIVE: This double-blind, placebo-controlled, dose-finding phase IIb study 
      evaluated the efficacy and safety of ponesimod, an oral selective S1P1 receptor 
      modulator, for the treatment of patients with relapsing-remitting multiple 
      sclerosis (RRMS). METHODS: 464 patients were randomised to receive once-daily 
      oral ponesimod 10, 20 or 40 mg, or placebo for 24 weeks. The primary endpoint was 
      the cumulative number of new T1 gadolinium-enhanced (T1 Gd+) lesions per patient 
      recorded every 4 weeks from weeks 12 to 24 after study drug initiation. Secondary 
      endpoints were the annualised confirmed relapse rate (ARR) and time to first 
      confirmed relapse. Safety and tolerability were also evaluated. RESULTS: The mean 
      cumulative number of new T1 Gd+ lesions at weeks 12-24 was significantly lower in 
      the ponesimod 10 mg (3.5; rate ratio (RR) 0.57; p=0.0318), 20 mg (1.1; RR 0.17; 
      p<0.0001) and 40 mg (1.4; RR 0.23; p<0.0001) groups compared with placebo (6.2). 
      The mean ARR was lower with 40 mg ponesimod versus placebo, with a maximum 
      reduction of 52% (0.25 vs 0.53; p=0.0363). The time to first confirmed relapse 
      was increased with ponesimod compared with placebo. The proportion of patients 
      with >/= 1 treatment-emergent adverse events (AEs) was similar across ponesimod 
      groups and the placebo group. Frequently reported AEs with higher incidence in 
      the three ponesimod groups compared with placebo were anxiety, dizziness, 
      dyspnoea, increased alanine aminotransferase, influenza, insomnia and peripheral 
      oedema. CONCLUSIONS: Once-daily treatment with ponesimod 10, 20 or 40 mg 
      significantly reduced the number of new T1 Gd+ lesions and showed a beneficial 
      effect on clinical endpoints. Ponesimod was generally well tolerated, and further 
      investigation of ponesimod for the treatment of RRMS is under consideration. 
      TRIAL REGISTRATION NUMBER: NCT01006265.
CI  - Published by the BMJ Publishing Group Limited. For permission to use (where not 
      already granted under a licence) please go to 
      http://group.bmj.com/group/rights-licensing/permissions.
FAU - Olsson, Tomas
AU  - Olsson T
AD  - Department of Clinical Neurosciences, Karolinska Institute, Stockholm, Sweden.
FAU - Boster, Aaron
AU  - Boster A
AD  - Ohio State University Multiple Sclerosis Centre, Columbus, Ohio, USA.
FAU - Fernandez, Oscar
AU  - Fernandez O
AD  - Hospital Regional Universitario Carlos Haya, Malaga, Spain.
FAU - Freedman, Mark S
AU  - Freedman MS
AD  - Multiple Sclerosis Research Unit, The Ottawa Hospital Research Institute, Ottawa, 
      Ohio, Canada.
FAU - Pozzilli, Carlo
AU  - Pozzilli C
AD  - Sapienza University of Rome, Rome, Italy.
FAU - Bach, Doris
AU  - Bach D
AD  - Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
FAU - Berkani, Ouali
AU  - Berkani O
AD  - Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
FAU - Mueller, Markus S
AU  - Mueller MS
AD  - Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
FAU - Sidorenko, Tatiana
AU  - Sidorenko T
AD  - Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
FAU - Radue, Ernst-Wilhelm
AU  - Radue EW
AD  - Medical Image Analysis Centre, University Hospital Basel, Basel, Switzerland.
FAU - Melanson, Maria
AU  - Melanson M
AD  - University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01006265
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20140321
PL  - England
TA  - J Neurol Neurosurg Psychiatry
JT  - Journal of neurology, neurosurgery, and psychiatry
JID - 2985191R
RN  - 0 (Receptors, Lysosphingolipid)
RN  - 0 (Thiazoles)
RN  - 5G7AKV2MKP (ponesimod)
SB  - IM
CIN - J Neurol Neurosurg Psychiatry. 2014 Nov;85(11):1180. PMID: 24659798
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis, Relapsing-Remitting/*drug therapy/pathology
MH  - Receptors, Lysosphingolipid/*antagonists & inhibitors
MH  - Severity of Illness Index
MH  - Thiazoles/administration & dosage/adverse effects/*therapeutic use
MH  - Young Adult
PMC - PMC4215282
OTO - NOTNLM
OT  - Multiple Sclerosis
EDAT- 2014/03/25 06:00
MHDA- 2015/01/27 06:00
PMCR- 2014/10/31
CRDT- 2014/03/25 06:00
PHST- 2014/03/25 06:00 [entrez]
PHST- 2014/03/25 06:00 [pubmed]
PHST- 2015/01/27 06:00 [medline]
PHST- 2014/10/31 00:00 [pmc-release]
AID - jnnp-2013-307282 [pii]
AID - 10.1136/jnnp-2013-307282 [doi]
PST - ppublish
SO  - J Neurol Neurosurg Psychiatry. 2014 Nov;85(11):1198-208. doi: 
      10.1136/jnnp-2013-307282. Epub 2014 Mar 21.