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Cardiac effects of amiselimod compared with fingolimod and placebo: results of a randomised, parallel-group, phase I study in healthy subjects.

Harada, T; Wilbraham, D; de La Borderie, G; Inoue, S; Bush, J; Camm, AJ (2017) Cardiac effects of amiselimod compared with fingolimod and placebo: results of a randomised, parallel-group, phase I study in healthy subjects. Br J Clin Pharmacol, 83 (5). pp. 1011-1027. ISSN 1365-2125 https://doi.org/10.1111/bcp.13203
SGUL Authors: Camm, Alan John

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Abstract

AIM: Amiselimod (MT-1303) is a selective sphingosine 1-phosphate 1 (S1P1 ) receptor modulator which is currently being developed for the treatment of various autoimmune diseases. Unlike some other S1P receptor modulators, amiselimod seemed to show a favourable cardiac safety profile in preclinical, phase I and II studies. The aim of the current study was to characterize the cardiac effects of amiselimod by directly comparing it with fingolimod and placebo. METHODS: A total of 81 healthy subjects aged 18-55 years were equally randomized to receive amiselimod 0.4 mg, amiselimod 0.8 mg, placebo or fingolimod 0.5 mg once daily for 28 days. The chronotropic/dromotropic and inotropic effects were evaluated using intensive Holter electrocardiogram and echocardiography. RESULTS: Unlike fingolimod, neither amiselimod dose exerted acute (1-6 h) negative chronotropic effects on Days 1 and 2. The lowest nadir mean hourly heart rate was observed on Day 14 in the amiselimod 0.4 mg group (least squares mean difference: -4.40 bpm, 95% confidence interval -7.15, -1.66) and Day 7 in the 0.8 mg group [-3.85 bpm (-6.58, -1.11)] compared with placebo, but these changes were smaller than those with fingolimod on Day 1 [-6.49 bpm (-8.95, -4.02)]. No clinically significant bradyarrhythmia or cardiac functional abnormalities were observed in either amiselimod group. Both amiselimod doses were well tolerated and no serious adverse events were reported. Fingolimod was also generally well tolerated, although one subject was withdrawn owing to highly frequent 2:1 atrioventricular blocks on Day 1. CONCLUSION: The study demonstrated a more favourable cardiac safety profile for amiselimod than fingolimod when administered over 28 days in healthy subjects.

Item Type: Article
Additional Information: © 2016 Mitsubishi Tanabe Pharma Europe Ltd. The British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Keywords: amiselimod (MT-1303), cardiac effects, fingolimod, healthy subject, sphingosine 1-phosphate, Pharmacology & Pharmacy, 1115 Pharmacology And Pharmaceutical Sciences
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cardiac (INCCCA)
Journal or Publication Title: Br J Clin Pharmacol
ISSN: 1365-2125
Language: eng
Dates:
DateEvent
24 April 2017Published
6 December 2016Published Online
1 December 2016Accepted
Publisher License: Creative Commons: Attribution-No Derivative Works 4.0
PubMed ID: 27921320
Go to PubMed abstract
URI: http://openaccess.sgul.ac.uk/id/eprint/108672
Publisher's version: https://doi.org/10.1111/bcp.13203

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