The novel phosphodiesterase inhibitor NM-702 improves claudication-limited exercise performance in patients with peripheral arterial disease.
OBJECTIVE
The current study tested the hypothesis that NM-702 improves treadmill exercise performance in peripheral arterial disease patients with claudication-limited exercise performance.


BACKGROUND
Patients with claudication experience significant disability, owing to their exercise limitation. Therapeutic options to improve exercise performance in these patients are limited. NM-702 is a novel drug that inhibits phosphodiesterase as well as thromboxane A2 synthase.


METHODS
This study was a randomized, multi-center, placebo-controlled, double-blind trial. Patients were randomized to receive 24 weeks of twice-daily treatment with either placebo (intent to treat population, n = 130), 4 mg NM-702 (n = 126), or 8 mg NM-702 (n = 130).


RESULTS
After 24 weeks of treatment, 8 mg NM-702 was associated with a statistically significant increased peak walking time on a graded treadmill as compared with placebo (p = 0.004). Peak walking time after 24 weeks was increased by 17.1 +/- 49.0% in the placebo arm, 22.1 +/- 60.1% in the 4-mg NM-702 arm, and 28.1 +/- 50.5% in the 8-mg NM-702 arm. NM-702 at the 8-mg dose for 24 weeks was associated with statistically significant improvements in the treadmill claudication onset time as compared with placebo. In addition, as compared with placebo, NM-702 improved the physical component and physical functioning scores of the Medical Outcomes Study 36-Item Short Form and the walking distance and stair climbing domains of the Walking Impairment Questionnaire. NM-702 was generally well tolerated, but adverse events typical of vasodilators were common.


CONCLUSIONS
NM-702 used for 24 weeks by patients with claudication was associated with improvements in laboratory- and ambulatory-based exercise performance.
Brass
Eric P
EP
Department of Medicine, Harbor-UCLA Medical Center, Torrance, California 90502, USA. ebrass@ucla.edu
Anthony
Richard
R
Cobb
Frederick R
FR
Koda
Isao
I
Jiao
Jenny
J
Hiatt
William R
WR
D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D006801:Humans; D007383:Intermittent Claudication / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000150:complications / Q000188:drug therapy*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011724:Pyridazines / Q000627:therapeutic use*
C516117:4-bromo-6-(3-(4-chlorophenyl)propoxy)-5-(3-pyridylmethylamino)-3(2H)-pyridazinone hydrochloride; D010726:Phosphodiesterase Inhibitors; D011724:Pyridazines