This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Norgren, L Search for Related Content PubMed PubMed Citation Articles by Norgren, L Social Bookmarking                   What's this?

Sarpogrelate, a 5-HT2A receptor antagonist in intermittent claudication. A Phase II European study

Department of Surgery, University Hospital, Örebro, Sweden, lars.norgren{at}orebroll.se

A Jawien

Department of Surgery, NCU, Collegium Medicum, Bydgoszcz, Poland

L Mátyás

Department of Surgery, BAZM Korhaz es Rendelointezet Angiologiai Osztaly, Miskolc, Hungary

H Rieger

Society for the Management of Vascular Diseases, Aggertalklinik, Engelskirchen, Germany

K Arita

Mitsubishi Pharma Corporation, Tokyo, Japan

European MCI-9042 Study Group

This was a multinational, multicentre, double-blind Phase II study in Europe to evaluate the efficacy and safety of two dose regimens (200 mg bid and 200 mg tid) of sarpogrelate (MCI-9042, 5-HT_2A receptor antagonist) compared to placebo in patients with stable, moderately severe intermittent claudication. Following a single-blind placebo run-in period of 6 weeks, 364 (309 male and 55 female) patients (59.2 ± 8.4 years, mean SD) were randomized to receive sarpogrelate 200 mg bid, 200 mg tid or placebo for 24 weeks with a follow-up of 8 weeks. The primary objective was the increase of absolute claudication distance (ACD) at the end of treatment (week 24) compared to placebo. Analysis of covariance (ANCOVA) was performed on the log-transformed percentage of baseline ACD: log_e (ACD/baseline). A responder analysis (defined as a 50% improvement in ACD) was also performed. There was a marked training/placebo effect on the ACD which persisted up to 16 weeks. At 24 weeks the primary objective did not reach statistical significance (200 mg bid vs placebo, p = 0.225; 200 mg tid vs placebo, p = 0.580). In the responder analysis, 200 mg bid showed a statistically significant difference vs placebo (p = 0.035). In the exploratory analysis with completers (patients completing all treadmill tests), there was a statistical difference in ACD/baseline change for 200 mg bid (p = 0.035) and in the responder analysis for 200 mg tid (p = 0.044) at 24 weeks compared to placebo. Both treatments showed a carry-over effect for ACD during the 8-week follow-up (weeks 28-32). The treatment was well tolerated and no clinically significant safety concerns were reported. In conclusion, the study results confirm that sarpogrelate is well tolerated and although the primary endpoint failed to reach statistical significance, the responder analysis showed an increased absolute walking distance, which makes a further trial warranted, including a larger population, and possibly also a longer treatment period.

Key Words: intermittent claudication • MCI-9042 • sarpogrelate • walking distance

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?