Randomized, placebo-controlled study of a selective PDE4 inhibitor in the treatment of asthma.
BACKGROUND
Phosphodiesterase-4 (PDE4) inhibitors have potential utility as a new therapeutic approach to improving symptoms and pulmonary function in asthma and COPD. This study evaluated the efficacy and safety of MK-0359, a selective and potent oral PDE4 inhibitor, in chronic asthma.


METHODS
Adults (N=88) with > or =1 year asthma history and an FEV(1) 50-80% predicted were randomized to double-blind treatment with MK-0359 (15mg/day) or placebo for 14 days, then crossed-over to the other treatment for 14 days. The primary endpoint was the change from baseline in FEV(1) at the end of each 2-week treatment period. Secondary and other endpoints included the changes from baseline in Daytime asthma symptom score, Nighttime asthma symptom score, Total daily beta-agonist use (puffs/day), AM and PM peak expiratory flow (PEF) and overall asthma-specific quality-of-life. Safety and tolerability were assessed by clinical adverse experiences.


RESULTS
MK-0359 significantly improved the primary endpoint (versus placebo): the least-squares mean difference in change from baseline in FEV(1) (L) was 0.09L (95% CI 0.01, 0.18). Endpoints of Daytime asthma symptom score, Nighttime asthma symptom score, Total daily beta-agonist use, AM PEF, PM PEF, and quality-of-life were also significantly improved. Nineteen patients (24.1%) on MK-0359 and 8 patients (10.4%) on placebo reported gastrointestinal clinical adverse experiences. Serious gastrointestinal clinical adverse experiences were reported in 3 patients while receiving MK-0359.


CONCLUSIONS
Over a 14-day treatment period, the oral PDE4 inhibitor MK-0359 improved lower airway function, symptoms and rescue medication use in chronic asthma, although at the expense of gastrointestinal adverse experiences. (Clinical trial registry number: NCT00482898.).
Lu
Susan
S
Merck Research Laboratories, Rahway, NJ 07065, USA. susan_lu@merck.com
Liu
Nancy
N
Dass
S Balachandra
SB
Reiss
Theodore F
TF
Knorr
Barbara A
BA
D015746:Abdominal Pain / Q000139:chemically induced; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D002908:Chronic Disease; D018592:Cross-Over Studies; D003967:Diarrhea / Q000139:chemically induced; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008297:Male; D010366:Peak Expiratory Flow Rate; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D018401:Sample Size; D016896:Treatment Outcome; D055815:Young Adult
D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors