title: Roflumilast for asthma: Safety findings from a pooled analysis of ten clinical studies.
abstract: BACKGROUND
  The safety profile of roflumilast, a phosphodiesterase 4 inhibitor, has been extensively researched in patients with chronic obstructive pulmonary disease (COPD). Adverse events (AEs) including headache, diarrhoea and weight loss have been reported. Much less is known about the safety of roflumilast treatment in patients with bronchial asthma.
  
  
  OBJECTIVE
  To evaluate the safety and tolerability of roflumilast using safety data from one open-label and ten pooled placebo-controlled phase II and III clinical studies completed between 1997 and 2005.
  
  
  METHODS
  The studies were conducted at sites in Europe, North and South America, Africa, Australasia and Asia and study length varied from 4 to 40 weeks. Data for 5169 patients between 12 and 70 years of age, of whom 2851 received roflumilast at doses of 125, 250 and 500 μg, were analyzed. At randomization patients had a forced expiratory flow of 45-100%.
  
  
  RESULTS
  Headache was the most frequent AE with an incidence rate of 50 and 29.2 per 100 patient-years in the 500 μg roflumilast and placebo groups, respectively. Gastrointestinal AEs were common. Nausea and diarrhoea occurred in 28.7 and 28.3 per 100 patient-years in the 500 μg roflumilast and placebo groups, respectively. The extent of weight loss in roflumilast-treated patients was small. AEs reported in 465 patients in the 4-week open-label follow-up study reflected those of the pooled studies.
  
  
  CONCLUSIONS
  The severity and incidence of AEs reported from this pooled safety analysis confirm that roflumilast is generally well tolerated by patients with asthma. This reflects the general safety profile reported previously in patients with COPD. All studies were funded by Takeda. Trial registration numbers available on ClinicalTrials.gov: NCT00073177, NCT00076076, NCT00163527.
authors.affiliation: Northeast Medical Research Associates, Dartmouth, MD, USA. Electronic address: pchervinsky@gmail.com.
authors.forename: P
authors.initials: P
authors.lastname: Chervinsky
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, University of California, San Diego, CA, USA. Electronic address: eliomeltzer@gmail.com.
authors.forename: E O
authors.initials: EO
authors.lastname: Meltzer
authors.affiliation: Division of Allergy and Immunology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA. Electronic address: wwb@medicine.wisc.edu.
authors.forename: W
authors.initials: W
authors.lastname: Busse
authors.affiliation: Department of Respiratory Medicine and Allergology, Tokyo National Hospital, Tokyo, Japan. Electronic address: kenohta@tokyo-hosp.jp.
authors.forename: K
authors.initials: K
authors.lastname: Ohta
authors.affiliation: Monash Lung & Sleep, Monash Medical Center and University, Victoria, Australia. Electronic address: philip.bardin@monash.edu.
authors.forename: P
authors.initials: P
authors.lastname: Bardin
authors.affiliation: Takeda Pharmaceuticals International GmbH, Zurich, Switzerland. Electronic address: dirk.bredenbroeker@takeda.com.
authors.forename: D
authors.initials: D
authors.lastname: Bredenbröker
authors.affiliation: Division of Pulmonology, Department of Medicine, University of Cape Town, Cape Town, South Africa. Electronic address: Eric.Bateman@uct.ac.za.
authors.forename: E D
authors.initials: ED
authors.lastname: Bateman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000631:Aminopyridines / Q000009:adverse effects*; D001249:Asthma / Q000188:drug therapy*; D001549:Benzamides / Q000009:adverse effects*; D002648:Child; D003521:Cyclopropanes / Q000009:adverse effects; D006801:Humans; D008875:Middle Aged; D058988:Phosphodiesterase 4 Inhibitors / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D000631:Aminopyridines; D001549:Benzamides; D003521:Cyclopropanes; D058988:Phosphodiesterase 4 Inhibitors; C424423:Roflumilast
keywords: Asthma; Placebo; Roflumilast; Safety