PMID- 27060836
OWN - NLM
STAT- MEDLINE
DCOM- 20171108
LR  - 20220408
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Print)
IS  - 0306-5251 (Linking)
VI  - 82
IP  - 2
DP  - 2016 Aug
TI  - COMPARE: Pharmacokinetic profiles of subcutaneous peginterferon beta-1a and 
      subcutaneous interferon beta-1a over 2 weeks in healthy subjects.
PG  - 380-8
LID - 10.1111/bcp.12968 [doi]
AB  - AIM: Subcutaneous (s.c.) peginterferon beta-1a injected once every 2 weeks and 
      s.c. interferon beta-1a injected three times per week (Rebif(R)) 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. METHODS: Thirty healthy 
      subjects received one dose of peginterferon beta-1a (125 mug s.c.) or six doses of 
      interferon beta-1a (44 mug 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. RESULTS: 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. CONCLUSIONS: 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.
CI  - (c) 2016 The British Pharmacological Society.
FAU - Hu, Xiao
AU  - Hu X
AD  - Biogen, Cambridge, MA, USA.
FAU - Shang, Shulian
AU  - Shang S
AD  - Biogen, Cambridge, MA, USA.
FAU - Nestorov, Ivan
AU  - Nestorov I
AD  - Biogen, Cambridge, MA, USA.
FAU - Hasan, Jawad
AU  - Hasan J
AD  - Biogen, Cambridge, MA, USA.
FAU - Seddighzadeh, Ali
AU  - Seddighzadeh A
AD  - Biogen, Cambridge, MA, USA.
FAU - Dawson, Katherine
AU  - Dawson K
AD  - Biogen, Cambridge, MA, USA.
FAU - Sperling, Bjorn
AU  - Sperling B
AD  - Biogen, Cambridge, MA, USA.
FAU - Werneburg, Brian
AU  - Werneburg B
AD  - Biogen, Cambridge, MA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02269930
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20160529
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Adjuvants, Immunologic)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 77238-31-4 (Interferon-beta)
RN  - I8309403R0 (peginterferon beta-1a)
RN  - XRO4566Q4R (Interferon beta-1a)
SB  - IM
MH  - Adjuvants, Immunologic/*administration & dosage/adverse effects/pharmacokinetics
MH  - Adolescent
MH  - Adult
MH  - Area Under Curve
MH  - Cross-Over Studies
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Interferon beta-1a/*administration & dosage/adverse effects/pharmacokinetics
MH  - Interferon-beta/*administration & dosage/adverse effects/pharmacokinetics
MH  - Male
MH  - Middle Aged
MH  - Polyethylene Glycols/*administration & dosage/adverse effects/pharmacokinetics
MH  - Young Adult
PMC - PMC4972154
OTO - NOTNLM
OT  - AUC
OT  - exposure
OT  - injection-site reactions
OT  - multiple sclerosis
OT  - pharmacokinetics
OT  - tolerability
EDAT- 2016/04/12 06:00
MHDA- 2017/11/09 06:00
PMCR- 2017/08/01
CRDT- 2016/04/11 06:00
PHST- 2015/12/01 00:00 [received]
PHST- 2016/03/09 00:00 [revised]
PHST- 2016/04/02 00:00 [accepted]
PHST- 2016/04/11 06:00 [entrez]
PHST- 2016/04/12 06:00 [pubmed]
PHST- 2017/11/09 06:00 [medline]
PHST- 2017/08/01 00:00 [pmc-release]
AID - BCP12968 [pii]
AID - 10.1111/bcp.12968 [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2016 Aug;82(2):380-8. doi: 10.1111/bcp.12968. Epub 2016 May 
      29.