Dataset Information

Effects of Subcutaneous Pasireotide on Cardiac Repolarization in Healthy Volunteers: a Single?Center, Phase I, Randomized, Four?Way Crossover Study.

ABSTRACT: The aim of this study was to evaluate the effects of subcutaneous pasireotide on cardiac repolarization in healthy volunteers. Healthy volunteers were randomized to one of four treatment sequences (n?=?112) involving four successive treatments in different order: pasireotide 600?µg (therapeutic dose) or 1,950?µg (maximum tolerated dose) bid by subcutaneous injection (sc), placebo injection and oral moxifloxacin. Maximum ??QTcI occurred 2 hours post-dose for both doses of pasireotide. Mean ??QTcI was 13.2?milliseconds (90% CI: 11.4, 15.0) and 16.1?milliseconds (90% CI: 14.3, 17.9) for the 600 and 1,950?µg bid doses, respectively. Maximal placebo-subtracted change in QTcI from baseline for moxifloxacin was 11.1 (90% CI: 9.3, 12.9) milliseconds. Both pasireotide doses caused a reduction in heart rate: maximal heart rate change compared with placebo occurred at 1?hour for pasireotide 600?µg bid and at 0.5?hours for pasireotide 1,950?µg bid, with heart rate reductions of 10.4 and 14.9?bpm, respectively. At the therapeutic dose of 600?µg, pasireotide has a modest QT-prolonging effect. The relatively small increase of ?3?milliseconds in ??QTcI in the presence of a 3.25-fold increase in dose suggests a relatively flat dose–effect relationship of pasireotide on ??QTcI in healthy volunteers. No safety concerns for pasireotide were identified during the study.

SUBMITTER: Breitschaft A

PROVIDER: S-EPMC4272414 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effects of Subcutaneous Pasireotide on Cardiac Repolarization in Healthy Volunteers: a Single‐Center, Phase I, Randomized, Four‐Way Crossover Study.

Breitschaft Astrid A Hu Ke K Darstein Christelle C Ligueros-Saylan Monica M Jordaan Pierre P Song Dongweon D Hudson Michelle M Shah Rashmi R

Journal of clinical pharmacology 20140101 1

The aim of this study was to evaluate the effects of subcutaneous pasireotide on cardiac repolarization in healthy volunteers. Healthy volunteers were randomized to one of four treatment sequences (n = 112) involving four successive treatments in different order: pasireotide 600 µg (therapeutic dose) or 1,950 µg (maximum tolerated dose) bid by subcutaneous injection (sc), placebo injection and oral moxifloxacin. Maximum ΔΔQTcI occurred 2 hours post-dose for both doses of pasireotide. Mean ΔΔQTcI ...[more]

PMID: 24242903

Similar Datasets

Project description:BackgroundPeginterferon 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.MethodsA 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 (Cmax) and area under the curve from time zero extrapolated to infinity (AUCinf). Other PK parameters, as well as PD (serum neopterin) and safety profiles, were also evaluated.ResultsThe study enrolled 136 participants. Bioequivalence of IM and SC peginterferon beta-1a was established for both Cmax ([least squares (LS)] mean IM/SC ratio: 1.083 [90% confidence interval (CI), 0.975-1.203]) and AUCinf (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).ConclusionsThese 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.

Dataset Information

Effects of Subcutaneous Pasireotide on Cardiac Repolarization in Healthy Volunteers: a Single?Center, Phase I, Randomized, Four?Way Crossover Study.

Publications

Effects of Subcutaneous Pasireotide on Cardiac Repolarization in Healthy Volunteers: a Single‐Center, Phase I, Randomized, Four‐Way Crossover Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets