MR889, a neutrophil elastase inhibitor, in patients with chronic obstructive pulmonary disease: a double-blind, randomized, placebo-controlled clinical trial.
We investigated whether MR889, a synthetic cyclic thiolic elastase inhibitor, administered for a period of 4 weeks to chronic obstructive pulmonary disease (COPD) patients, is well-tolerated, and whether it modifies biochemical indices of lung destruction. The study was a double-blind, randomized, placebo-controlled clinical trial in COPD patients. Thirty subjects were administered MR889 orally at a dose of 500 mg b.i.d. for 4 weeks, and 30 received placebo following the same schedule. In addition to safety parameters, MR889 efficacy was checked by a pretreatment/postreatment evaluation of levels of plasma elastin-derived peptides and urinary desmosine. There were no statistically significant differences between pretreatment and posttreatment efficacy parameter levels either in the control group or in the treated group. However, in a subset of treated patients with a short disease duration, the level of urinary desmosine dropped significantly with respect to pretreatment values (p = 0.004). We conclude that MR889 is safe to administer to COPD patients for a period of at least 4 weeks. During this time, MR889 does not modify biochemical markers of lung destruction in unselected COPD patients. Nevertheless, a subset of treated patients with fairly short disease duration showed a post-treatment reduction of desmosine urine levels, thus justifying the need for further studies to prove the efficacy of MR889 in modulating indices of lung destruction in COPD.
Luisetti
M
M
Istituto di Tisiologia e Malattie Respiratorie, Università di Pavia, IRCCS Policlinico San Matteo, Italy.
Sturani
C
C
Sella
D
D
Madonini
E
E
Galavotti
V
V
Bruno
G
G
Peona
V
V
Kucich
U
U
Dagnino
G
G
Rosenbloom
J
J
Starcher
B
B
Grassi
C
C
D000368:Aged; D003895:Desmosine / Q000652:urine; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004549:Elastin / Q000097:blood; D005260:Female; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D008173:Lung Diseases, Obstructive / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D013876:Thiophenes / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors
D011480:Protease Inhibitors; D013876:Thiophenes; D003895:Desmosine; D004549:Elastin; C062051:midesteine; D019272:Leukocyte Elastase