Randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of AS-013, a prostaglandin E-1 prodrug, in patients with intermittent claudication

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 E-1 have been disappointing. This is the first report of a controlled clinical trial of AS-013, a novel prodrug of prostaglandin E-1 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 greater than or equal to 30 and less than or equal to 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. 3.5 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 E-1, 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.