Dataset Information

Bioequivalence of intramuscular and subcutaneous peginterferon beta-1a: results of a phase I, open-label crossover study in healthy volunteers.

ABSTRACT:

Background

Peginterferon beta-1a administered every 2 weeks via subcutaneous (SC) injection is approved to treat adult patients with relapsing-remitting multiple sclerosis (RRMS) and relapsing forms of multiple sclerosis (RMS). However, associated injection site reactions (ISRs) can lead to treatment discontinuation. Prior studies with interferon beta-1a reported a lower frequency of ISRs with intramuscular (IM) administration than with SC administration. IM administration of peginterferon beta-1a may therefore represent a useful alternative treatment option.

Methods

A phase?I, open-label, two-period crossover study randomized healthy volunteers to receive a single dose of peginterferon beta-1a 125?mcg administered IM followed by a single 125?mcg dose administered SC after a 28-day washout or vice versa. Blood samples were collected up to 504?h post dose to determine pharmacokinetic (PK) and pharmacodynamic (PD) profiles. The primary endpoint was assessment of bioequivalence based on maximum serum concentration (C_max) and area under the curve from time zero extrapolated to infinity (AUC_inf). Other PK parameters, as well as PD (serum neopterin) and safety profiles, were also evaluated.

Results

The study enrolled 136 participants. Bioequivalence of IM and SC peginterferon beta-1a was established for both C_max ([least squares (LS)] mean IM/SC ratio: 1.083 [90% confidence interval (CI), 0.975-1.203]) and AUC_inf (LS mean IM/SC ratio: 1.089 [90% CI, 1.020-1.162]). Other PK and PD parameters were similar between administration routes, although moderate to high inter-subject variability was observed for IM and SC. Safety profiles were generally balanced between IM and SC administration. ISRs occurred at a lower frequency with IM [14.4% (95% CI, 8.89-21.56%)] than with SC [32.1% (95% CI, 24.29-40.70%)] administration (p?=?0.0005).

Conclusions

These results demonstrate bioequivalence between peginterferon beta-1a IM and SC and support the consideration of IM injection of peginterferon beta-1a as a viable treatment option in patients with RRMS and RMS.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC7883310 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Bioequivalence of intramuscular and subcutaneous peginterferon beta-1a: results of a phase I, open-label crossover study in healthy volunteers.

Zhao Yuan Y Chen Kun K Ramia Nancy N Sahu Sangeeta S Kumar Achint A Naylor Maria L ML Zhu Li L Naik Himanshu H Butts Cherié L CL

Therapeutic advances in neurological disorders 20210122

<h4>Background</h4>Peginterferon beta-1a administered every 2 weeks <i>via</i> subcutaneous (SC) injection is approved to treat adult patients with relapsing-remitting multiple sclerosis (RRMS) and relapsing forms of multiple sclerosis (RMS). However, associated injection site reactions (ISRs) can lead to treatment discontinuation. Prior studies with interferon beta-1a reported a lower frequency of ISRs with intramuscular (IM) administration than with SC administration. IM administration of pegi ...[more]

PMID: 33628334

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Dataset Information

Bioequivalence of intramuscular and subcutaneous peginterferon beta-1a: results of a phase I, open-label crossover study in healthy volunteers.

Background

Methods

Results

Conclusions

Publications

Bioequivalence of intramuscular and subcutaneous peginterferon beta-1a: results of a phase I, open-label crossover study in healthy volunteers.

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