MR889, a neutrophil elastase inhibitor, in patients with chronic obstructive pulmonary disease: a double-blind, randomized, placebo-controlled clinical trial.

Abstract

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.

• Authors: M Luisetti, C Sturani, D Sella, E Madonini, V Galavotti, G Bruno, V Peona, U Kucich, G Dagnino, J Rosenbloom, B Starcher, C Grassi
• Journal: The European respiratory journal (Eur Respir J) Vol. 9 Issue 7 Pg. 1482-6 (Jul 1996) ISSN: 0903-1936 [Print] England
• PMID: 8836663 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Protease Inhibitors
• Thiophenes
• Desmosine
• Elastin
• midesteine
• Leukocyte Elastase

Topics

• Aged
• Desmosine (urine)
• Double-Blind Method
• Drug Administration Schedule
• Elastin (blood)
• Female
• Humans
• Leukocyte Elastase (antagonists & inhibitors)
• Lung Diseases, Obstructive (drug therapy, metabolism)
• Male
• Protease Inhibitors (administration & dosage, therapeutic use)
• Thiophenes (administration & dosage, therapeutic use)
• Time Factors