title: A phase 1 study evaluating the pharmacokinetics, safety and tolerability of repeat dosing with a human IL-13 antibody (CAT-354) in subjects with asthma.
abstract: BACKGROUND
  IL-13 has been implicated in the development of airway inflammation and hyperresponsiveness. This study investigated the multiple-dose pharmacokinetics and safety profile of human anti-IL-13 antibody (CAT-354) in adults with asthma.
  
  
  METHODS
  This was a multiple-dose, randomised, double-blind, placebo-controlled phase 1 study in asthmatics (forced expiratory volume in 1 second [FEV1] >or= 80% predicted). Subjects were randomised to receive three intravenous infusions of CAT-354 (1 mg/kg, 5 mg/kg or 10 mg/kg) or placebo at 28-day intervals. Blood samples were taken for pharmacokinetic measurements. Safety was assessed by adverse events, vital signs, ECGs, laboratory and pulmonary function parameters.
  
  
  RESULTS
  Twenty-three subjects (aged 21-60 years, FEV1 88-95% predicted) received >or= 1 dose of study medication. The half-life of CAT-354 was 12-17 days and was dose-independent. The maximum serum concentration and area under the curve were dose-dependent. Clearance (2.2-2.6 mL/day/kg) and volume of distribution (44-57 mL/kg) were both low and dose-independent. The observed maximum serum concentration after each dose increased slightly from dose 1 through dose 3 at all dose levels, consistent with an accumulation ratio of 1.4 to 1.7 for area under the curve. Most adverse events were deemed mild to moderate and unrelated to study medication. One SAE was reported and deemed unrelated to study drug. There were no effects of clinical concern for vital signs, ECG, laboratory or pulmonary parameters.
  
  
  CONCLUSIONS
  CAT-354 exhibited linear pharmacokinetics and an acceptable safety profile. These findings suggest that at the doses tested, CAT-354 can be safely administered in multiple doses to patients with asthma.
  
  
  BACKGROUND
  NCT00974675.
authors.affiliation: Medicines Evaluation Unit, University Hospital of South Manchester Foundation Trust, University of Manchester, Manchester, UK
authors.forename: Dave
authors.initials: D
authors.lastname: Singh
authors.forename: Binita
authors.initials: B
authors.lastname: Kane
authors.forename: Nestor A
authors.initials: NA
authors.lastname: Molfino
authors.forename: Raffaella
authors.initials: R
authors.lastname: Faggioni
authors.forename: Lorin
authors.initials: L
authors.lastname: Roskos
authors.forename: Ashley
authors.initials: A
authors.lastname: Woodcock
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000009:adverse effects; D018793:Interleukin-13 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D018793:Interleukin-13