Randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of AS-013, a prostaglandin E1 prodrug, in patients with intermittent claudication

J. J. F. Belch, P. R. F. Bell, D. Creissen, John A. Dormandy, R. C. Kester, R. D. McCollum, Y. Mizushima, C. V. Ruckley, J. H. Scurr, J. H. N. Wolfe

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    Abstract

    Background Intermittent claudication due to peripheral arterial occlusive disease (PAOD) is a common cause of pain and disability in the middle-aged. Clinical trials of the potent vasodilator prostaglandin E1 have been disappointing. This is the first report of a controlled clinical trial of AS-013, a novel prodrug of prostaglandin E1 incorporated into lipid microspheres that has been developed to improve delivery of the active compound to blood vessel walls.

    Methods and Results Eighty patients with stenosis or occlusion, symptoms of intermittent claudication, and maximum walking distance of >=30 and <=300 m on a standard treadmill test were randomized to placebo or one of three dosage regimens of AS-013. Drug was administered by intravenous injection 5 d/wk for 4 weeks. Treadmill tests and other assessments were completed at weeks 0, 4, and 8. A statistically significant increase in maximum walking distance was observed at 4 weeks (for placebo: median, 4.5 m; interquartile range [IQR], 20; for active treatment: median, 28.0 m; IQR, 81; P<.01, Mann-Whitney test). A similar response was seen at 8 weeks (for placebo: median, -11.2 m; IQR, 35; for active treatment: median, 35 m; IQR, 68; P<.01, Mann-Whitney test).
    Dose-related improvements in pain-free walking distance and quality of life were observed. No serious safety issues were noted.

    Conclusions These promising clinical data indicate that AS-013, a new prodrug of prostaglandin E1, could provide an effective and acceptable treatment for patients with intermittent claudication. Studies to investigate the optimal dosing regimen, duration of clinical benefit, and effects in more severe forms of peripheral arterial disease are warranted.

    Original languageEnglish
    Pages (from-to)2298-2302
    Number of pages5
    JournalCirculation
    Volume95
    Issue number9
    Publication statusPublished - 6 May 1997

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    Intermittent Claudication
    Alprostadil
    Prodrugs
    Walking
    Peripheral Arterial Disease
    Placebos
    Exercise Test
    Safety
    Arterial Occlusive Diseases
    Controlled Clinical Trials
    Vasodilator Agents
    Microspheres
    Intravenous Injections
    Blood Vessels
    Pathologic Constriction
    Therapeutics
    Quality of Life
    Clinical Trials
    Lipids
    Pain

    Cite this

    Belch, J. J. F., Bell, P. R. F., Creissen, D., Dormandy, J. A., Kester, R. C., McCollum, R. D., ... Wolfe, J. H. N. (1997). Randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of AS-013, a prostaglandin E1 prodrug, in patients with intermittent claudication. Circulation, 95(9), 2298-2302.
    Belch, J. J. F. ; Bell, P. R. F. ; Creissen, D. ; Dormandy, John A. ; Kester, R. C. ; McCollum, R. D. ; Mizushima, Y. ; Ruckley, C. V. ; Scurr, J. H. ; Wolfe, J. H. N. / Randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of AS-013, a prostaglandin E1 prodrug, in patients with intermittent claudication. In: Circulation. 1997 ; Vol. 95, No. 9. pp. 2298-2302.
    @article{69548f9967a14706b5ba8a53805a072a,
    title = "Randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of AS-013, a prostaglandin E1 prodrug, in patients with intermittent claudication",
    abstract = "Background Intermittent claudication due to peripheral arterial occlusive disease (PAOD) is a common cause of pain and disability in the middle-aged. Clinical trials of the potent vasodilator prostaglandin E1 have been disappointing. This is the first report of a controlled clinical trial of AS-013, a novel prodrug of prostaglandin E1 incorporated into lipid microspheres that has been developed to improve delivery of the active compound to blood vessel walls. Methods and Results Eighty patients with stenosis or occlusion, symptoms of intermittent claudication, and maximum walking distance of >=30 and <=300 m on a standard treadmill test were randomized to placebo or one of three dosage regimens of AS-013. Drug was administered by intravenous injection 5 d/wk for 4 weeks. Treadmill tests and other assessments were completed at weeks 0, 4, and 8. A statistically significant increase in maximum walking distance was observed at 4 weeks (for placebo: median, 4.5 m; interquartile range [IQR], 20; for active treatment: median, 28.0 m; IQR, 81; P<.01, Mann-Whitney test). A similar response was seen at 8 weeks (for placebo: median, -11.2 m; IQR, 35; for active treatment: median, 35 m; IQR, 68; P<.01, Mann-Whitney test). Dose-related improvements in pain-free walking distance and quality of life were observed. No serious safety issues were noted. Conclusions These promising clinical data indicate that AS-013, a new prodrug of prostaglandin E1, could provide an effective and acceptable treatment for patients with intermittent claudication. Studies to investigate the optimal dosing regimen, duration of clinical benefit, and effects in more severe forms of peripheral arterial disease are warranted.",
    author = "Belch, {J. J. F.} and Bell, {P. R. F.} and D. Creissen and Dormandy, {John A.} and Kester, {R. C.} and McCollum, {R. D.} and Y. Mizushima and Ruckley, {C. V.} and Scurr, {J. H.} and Wolfe, {J. H. N.}",
    year = "1997",
    month = "5",
    day = "6",
    language = "English",
    volume = "95",
    pages = "2298--2302",
    journal = "Circulation",
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    }

    Belch, JJF, Bell, PRF, Creissen, D, Dormandy, JA, Kester, RC, McCollum, RD, Mizushima, Y, Ruckley, CV, Scurr, JH & Wolfe, JHN 1997, 'Randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of AS-013, a prostaglandin E1 prodrug, in patients with intermittent claudication', Circulation, vol. 95, no. 9, pp. 2298-2302.

    Randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of AS-013, a prostaglandin E1 prodrug, in patients with intermittent claudication. / Belch, J. J. F.; Bell, P. R. F.; Creissen, D.; Dormandy, John A.; Kester, R. C.; McCollum, R. D.; Mizushima, Y.; Ruckley, C. V.; Scurr, J. H.; Wolfe, J. H. N.

    In: Circulation, Vol. 95, No. 9, 06.05.1997, p. 2298-2302.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of AS-013, a prostaglandin E1 prodrug, in patients with intermittent claudication

    AU - Belch, J. J. F.

    AU - Bell, P. R. F.

    AU - Creissen, D.

    AU - Dormandy, John A.

    AU - Kester, R. C.

    AU - McCollum, R. D.

    AU - Mizushima, Y.

    AU - Ruckley, C. V.

    AU - Scurr, J. H.

    AU - Wolfe, J. H. N.

    PY - 1997/5/6

    Y1 - 1997/5/6

    N2 - Background Intermittent claudication due to peripheral arterial occlusive disease (PAOD) is a common cause of pain and disability in the middle-aged. Clinical trials of the potent vasodilator prostaglandin E1 have been disappointing. This is the first report of a controlled clinical trial of AS-013, a novel prodrug of prostaglandin E1 incorporated into lipid microspheres that has been developed to improve delivery of the active compound to blood vessel walls. Methods and Results Eighty patients with stenosis or occlusion, symptoms of intermittent claudication, and maximum walking distance of >=30 and <=300 m on a standard treadmill test were randomized to placebo or one of three dosage regimens of AS-013. Drug was administered by intravenous injection 5 d/wk for 4 weeks. Treadmill tests and other assessments were completed at weeks 0, 4, and 8. A statistically significant increase in maximum walking distance was observed at 4 weeks (for placebo: median, 4.5 m; interquartile range [IQR], 20; for active treatment: median, 28.0 m; IQR, 81; P<.01, Mann-Whitney test). A similar response was seen at 8 weeks (for placebo: median, -11.2 m; IQR, 35; for active treatment: median, 35 m; IQR, 68; P<.01, Mann-Whitney test). Dose-related improvements in pain-free walking distance and quality of life were observed. No serious safety issues were noted. Conclusions These promising clinical data indicate that AS-013, a new prodrug of prostaglandin E1, could provide an effective and acceptable treatment for patients with intermittent claudication. Studies to investigate the optimal dosing regimen, duration of clinical benefit, and effects in more severe forms of peripheral arterial disease are warranted.

    AB - Background Intermittent claudication due to peripheral arterial occlusive disease (PAOD) is a common cause of pain and disability in the middle-aged. Clinical trials of the potent vasodilator prostaglandin E1 have been disappointing. This is the first report of a controlled clinical trial of AS-013, a novel prodrug of prostaglandin E1 incorporated into lipid microspheres that has been developed to improve delivery of the active compound to blood vessel walls. Methods and Results Eighty patients with stenosis or occlusion, symptoms of intermittent claudication, and maximum walking distance of >=30 and <=300 m on a standard treadmill test were randomized to placebo or one of three dosage regimens of AS-013. Drug was administered by intravenous injection 5 d/wk for 4 weeks. Treadmill tests and other assessments were completed at weeks 0, 4, and 8. A statistically significant increase in maximum walking distance was observed at 4 weeks (for placebo: median, 4.5 m; interquartile range [IQR], 20; for active treatment: median, 28.0 m; IQR, 81; P<.01, Mann-Whitney test). A similar response was seen at 8 weeks (for placebo: median, -11.2 m; IQR, 35; for active treatment: median, 35 m; IQR, 68; P<.01, Mann-Whitney test). Dose-related improvements in pain-free walking distance and quality of life were observed. No serious safety issues were noted. Conclusions These promising clinical data indicate that AS-013, a new prodrug of prostaglandin E1, could provide an effective and acceptable treatment for patients with intermittent claudication. Studies to investigate the optimal dosing regimen, duration of clinical benefit, and effects in more severe forms of peripheral arterial disease are warranted.

    M3 - Article

    VL - 95

    SP - 2298

    EP - 2302

    JO - Circulation

    JF - Circulation

    SN - 0009-7322

    IS - 9

    ER -