phase II dose-ranging study of the phosphodiesterase inhibitor K-134 in patients with peripheral artery disease and claudication


A phase II dose-ranging study of the phosphodiesterase inhibitor K-134 in patients with peripheral artery disease and claudication


Brass EP, Cooper LT, Morgan RE, et al (Harbor-UCLA Ctr for Clinical Pharmacology, Torrance; Mayo Clinic, Rochester, MN; Kowa Res Inst, Morrisville, NC; et al) J Vasc Surg 55:381-389.e1, 2012§



J.D. Raffetto, MD



Evidence Ranking


A



Expert Rating


2



Abstract





Results


As determined by the prospectively defined adaptive criteria, the 25-mg K-134 arm was discontinued after 42 individuals had been randomized to the arm. During the 26-week treatment period, PWT increased by 23%, 33%, 37%, and 46% in the placebo, 50-mg K-134, 100-mg K-134, and cilostazol arms, respectively (primary analysis placebo vs 100-mg K-134 arm not statistically significant, P = .089). Secondary analyses showed that cilostazol significantly increased PWT after 14 weeks of treatment and that the 100-mg K-134 dose and cilostazol both increased PWT vs placebo after 14 and 26 weeks in those individuals who completed the 26-week trial and were compliant with the study drug, or when the data were analyzed using a mixed-effects model incorporating all time points. K-134 had tolerability and adverse effect profiles similar to that of cilostazol. Both drugs were associated with an increase in withdrawals before study completion due to adverse events compared with placebo.



Conclusions


K-134 was generally well tolerated. K-134 at a dose of 100 mg twice daily did not affect PWT according to the primary analysis, but K-134 and cilostazol both increased PWT when analyzed using a mixed-effects model and in the per-protocol population (Tables 1–4).



Table 1


Demographics of Study Patientsa


image


ABI, Ankle-brachial index; COT, claudication onset time; PWT, peak walking time.


aMean data are shown with the range or standard deviation. Data are for the modified intention-to-treat population, except for the 25-mg K-134 arm, for which data are from all randomized subjects. Data by country includes the modified intention-to-treat population and the 42 subjects randomized to 25 mg of K-134. P values for continuous variables were calculated from a one-way analysis of variance, and the χ2 test was used for categoric variables.


bFor differences between treatment arms.


cFor differences between countries.

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Apr 3, 2017 | Posted by in CARDIOLOGY | Comments Off on phase II dose-ranging study of the phosphodiesterase inhibitor K-134 in patients with peripheral artery disease and claudication

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