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Clinical Trial
. 2016 Aug;82(2):380-8.
doi: 10.1111/bcp.12968. Epub 2016 May 29.

COMPARE: Pharmacokinetic Profiles of Subcutaneous Peginterferon beta-1a and Subcutaneous Interferon beta-1a Over 2 Weeks in Healthy Subjects

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Free PMC article
Clinical Trial

COMPARE: Pharmacokinetic Profiles of Subcutaneous Peginterferon beta-1a and Subcutaneous Interferon beta-1a Over 2 Weeks in Healthy Subjects

Xiao Hu et al. Br J Clin Pharmacol. .
Free PMC article

Abstract

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 (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.

Trial registration: ClinicalTrials.gov NCT02269930.

Keywords: AUC; exposure; injection-site reactions; multiple sclerosis; pharmacokinetics; tolerability.

Figures

Figure 1
Figure 1
Study design. S.c. subcutaneous
Figure 2
Figure 2
Peginterferon beta‐1a and interferon beta‐1a serum concentration ±SE over 2 weeks. Dashed lines represent lower limit of quantification (15 pg ml–1 for s.c. peginterferon beta‐1a; 6 pg ml–1 for s.c. interferon beta‐1a); *n = 27 for doses 1–4 and n = 26 for doses 5–6. S.c., subcutaneous; SE, standard error. formula image s.c. peginterferon beta‐1a (n = 26), formula image s.c interferon beta‐1a (n = 26–27*)
Figure 3
Figure 3
Incidence (A) and frequency (B) of AEs related to study drug occuring in >10% of subjects following either treatment (formula image) s.c. peginterferon beta‐1a (n = 29), (formula image) s.c. interferon beta‐1a (n = 29). AE, adverse event; s.c., subcutaneous

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