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

L. Norgren, A. Jawien, L. Matyas, H. Rieger, K. Arita, J. J. F. Belch, European MCI-9042 Study Group

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    Abstract

    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-HT2A 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.

    Original languageEnglish
    Pages (from-to)75-83
    Number of pages9
    JournalVascular Medicine
    Volume11
    Issue number2
    DOIs
    Publication statusPublished - 2006

    Keywords

    • TRIAL
    • sarpogrelate
    • walking distance
    • QUALITY-OF-LIFE
    • MULTICENTER
    • ISCHEMIA
    • CILOSTAZOL
    • PERIPHERAL ARTERIAL-DISEASE
    • MCI-9042
    • NAFTIDROFURYL
    • RECEPTOR
    • EFFICACY
    • intermittent claudication

    Cite this

    Norgren, L., Jawien, A., Matyas, L., Rieger, H., Arita, K., Belch, J. J. F., & European MCI-9042 Study Group (2006). Sarpogrelate, a 5-HT2A receptor antagonist in intermittent claudication. A Phase II European study. Vascular Medicine, 11(2), 75-83. https://doi.org/10.1191/1358863x06vm657oa
    Norgren, L. ; Jawien, A. ; Matyas, L. ; Rieger, H. ; Arita, K. ; Belch, J. J. F. ; European MCI-9042 Study Group. / Sarpogrelate, a 5-HT2A receptor antagonist in intermittent claudication. A Phase II European study. In: Vascular Medicine. 2006 ; Vol. 11, No. 2. pp. 75-83.
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    author = "L. Norgren and A. Jawien and L. Matyas and H. Rieger and K. Arita and Belch, {J. J. F.} and {European MCI-9042 Study Group}",
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    Norgren, L, Jawien, A, Matyas, L, Rieger, H, Arita, K, Belch, JJF & European MCI-9042 Study Group 2006, 'Sarpogrelate, a 5-HT2A receptor antagonist in intermittent claudication. A Phase II European study', Vascular Medicine, vol. 11, no. 2, pp. 75-83. https://doi.org/10.1191/1358863x06vm657oa

    Sarpogrelate, a 5-HT2A receptor antagonist in intermittent claudication. A Phase II European study. / Norgren, L.; Jawien, A.; Matyas, L.; Rieger, H.; Arita, K.; Belch, J. J. F. ; European MCI-9042 Study Group.

    In: Vascular Medicine, Vol. 11, No. 2, 2006, p. 75-83.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Sarpogrelate, a 5-HT2A receptor antagonist in intermittent claudication. A Phase II European study

    AU - Norgren, L.

    AU - Jawien, A.

    AU - Matyas, L.

    AU - Rieger, H.

    AU - Arita, K.

    AU - Belch, J. J. F.

    AU - European MCI-9042 Study Group

    PY - 2006

    Y1 - 2006

    N2 - 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-HT2A 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.

    AB - 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-HT2A 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.

    KW - TRIAL

    KW - sarpogrelate

    KW - walking distance

    KW - QUALITY-OF-LIFE

    KW - MULTICENTER

    KW - ISCHEMIA

    KW - CILOSTAZOL

    KW - PERIPHERAL ARTERIAL-DISEASE

    KW - MCI-9042

    KW - NAFTIDROFURYL

    KW - RECEPTOR

    KW - EFFICACY

    KW - intermittent claudication

    U2 - 10.1191/1358863x06vm657oa

    DO - 10.1191/1358863x06vm657oa

    M3 - Article

    VL - 11

    SP - 75

    EP - 83

    JO - Vascular Medicine

    JF - Vascular Medicine

    SN - 1358-863X

    IS - 2

    ER -