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COMPARE: Pharmacokinetic profiles of subcutaneous peginterferon beta‐1a and subcutaneous interferon beta‐1a over 2 weeks in healthy subjects
Author(s) -
Hu Xiao,
Shang Shulian,
Nestorov Ivan,
Hasan Jawad,
Seddighzadeh Ali,
Dawson Katherine,
Sperling Bjørn,
Werneburg Brian
Publication year - 2016
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12968
Subject(s) - tolerability , medicine , pharmacokinetics , gastroenterology , confidence interval , crossover study , myalgia , adverse effect , interferon beta 1a , population , pharmacology , chills , bioequivalence , interferon , immunology , pathology , placebo , interferon beta , alternative medicine , environmental health
Aim 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. Methods 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 (AUC 0‐336h ) over 2 weeks and maximum observed serum concentrations ( C max ) were estimated using a non‐compartmental analysis. Results The PK analysis population comprised 26 subjects for each treatment. Drug exposure (AUC 0‐336h ) 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.