title: COMPARE: Pharmacokinetic profiles of subcutaneous peginterferon beta-1a and subcutaneous interferon beta-1a over 2 weeks in healthy subjects.
abstract: Subcutaneous (s.c.) peginterferon beta-1a injected once every 2 weeks and s.c. interferon beta-1a injected three times per week (Rebif®) have demonstrated efficacy in relapsing-remitting multiple sclerosis, but direct comparisons of pharmacological activity and tolerability between the two products are lacking. COMPARE was an open label, crossover, pharmacokinetic (PK) study evaluating drug exposure and the safety and tolerability of s.c. peginterferon beta-1a and s.c. interferon beta-1a, over 2 weeks in healthy subjects.
  
  
  
  Thirty healthy subjects received one dose of peginterferon beta-1a (125 μg s.c.) or six doses of interferon beta-1a (44 μg s.c.) over 2 weeks, followed by the alternate treatment after a 2 week washout period. Drug concentrations were measured using an enzyme-linked immunosorbent assay (ELISA) and PK parameters including cumulative area under the concentration-time curve (AUC0-336h ) over 2 weeks and maximum observed serum concentrations (Cmax ) were estimated using a non-compartmental analysis.
  
  
  
  The PK analysis population comprised 26 subjects for each treatment. Drug exposure (AUC0-336h ) was 60% higher with s.c. peginterferon than with s.c. interferon beta-1a (117.4 ng ml(-1) h, 95% confidence interval 95.6, 144.3 vs. 73.1 ng ml(-1) h, 95% confidence interval 61.2, 87.3, respectively; P < 0.0001). Injection-site reactions (ISRs) were the most common adverse events (AEs) observed with both treatments. Numerically lower frequencies and incidence rates of ISRs, headache, myalgia and chills were observed with s.c. peginterferon beta-1a.
  
  
  
  One dose of s.c. peginterferon delivered significantly greater drug exposure than s.c. interferon beta-1a three times a week over 2 weeks, and a lower frequency of AEs.
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Hu
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Shulian
authors.initials: S
authors.lastname: Shang
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Nestorov
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Jawad
authors.initials: J
authors.lastname: Hasan
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Seddighzadeh
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Dawson
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Sperling
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Werneburg
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D000068556:Interferon beta-1a / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016899:Interferon-beta / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D011092:Polyethylene Glycols; D016899:Interferon-beta; C428112:peginterferon beta-1a; D000068556:Interferon beta-1a
keywords: AUC; exposure; injection-site reactions; multiple sclerosis; pharmacokinetics; tolerability