Key result
A single dose of subcutaneous peginterferon beta-1a delivered 60.6% greater drug exposure over 2 weeks compared to six doses of subcutaneous interferon beta-1a.
Why the study?
Does one dose of s.c. peginterferon beta-1a provide greater drug exposure than six doses of s.c. interferon beta-1a over 2 weeks in healthy subjects?
RCT (n=30)
Open-label
Block randomization
No
Does one dose of s.c. peginterferon beta-1a provide greater drug exposure than six doses of s.c. interferon beta-1a over 2 weeks in healthy subjects?
Effect estimate: 60.6% higher
Absolute Event Rate: 117.4% vs 73.1%
p-value: p=<0.0001
A single dose of subcutaneous peginterferon beta-1a provides significantly greater drug exposure and a lower frequency of adverse events compared to six doses of interferon beta-1a over 2 weeks in healthy subjects.
Supports exploration of extended dosing intervals; leaves open clinical translation in multiple sclerosis.
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.
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Hu et al. (2016) conducted an RCT in Healthy subjects (n=30). Subcutaneous peginterferon beta-1a vs. Subcutaneous interferon beta-1a 44 μg three times per week was evaluated on Cumulative area under the concentration-time curve (AUC0-336h) over 2 weeks (60.6% higher, p=<0.0001). A single dose of subcutaneous peginterferon beta-1a delivered 60.6% greater drug exposure over 2 weeks compared to six doses of subcutaneous interferon beta-1a.
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