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Int. J. Mol. Sci. 2017, 18(12), 2636; https://doi.org/10.3390/ijms18122636

Pharmacokinetics, Pharmacodynamics, Tolerability, and Food Effect of Cenerimod, a Selective S1P1 Receptor Modulator in Healthy Subjects

1
Department of Clinical Pharmacology, Idorsia Pharmaceuticals Ltd., Allschwil 4123, Switzerland
2
Quintiles Drug Research Unit, London SE1 1YR, UK
3
Simbec Research Ltd., Merthyr Tydfil CF48 4DR, UK
4
Department of Global Drug Safety, Actelion Pharmaceuticals Ltd., Allschwil 4123, Switzerland
*
Author to whom correspondence should be addressed.
Received: 31 October 2017 / Revised: 28 November 2017 / Accepted: 1 December 2017 / Published: 6 December 2017
(This article belongs to the Special Issue Sphingolipids: Signals and Disease)
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Abstract

The pharmacokinetics, pharmacodynamics, tolerability, and food effect of cenerimod, a potent sphingosine-1-phosphate subtype 1 receptor modulator, were investigated in three sub-studies. Two double-blind, placebo-controlled, randomised studies in healthy male subjects were performed. Cenerimod was administered either as single dose (1, 3, 10 or 25 mg; Study 1) or once daily for 35 days (0.5, 1, 2 or 4 mg; Study 2). A two-period cross-over, open-label study was performed to assess the food effect (1 mg, Study 3). The pharmacokinetic profile of cenerimod was characterised by a tmax of 5.0–6.2 h. Terminal half-life after single and multiple doses ranged from 170 to 199 h and 283 to 539 h, respectively. Food had no relevant effect on the pharmacokinetics of cenerimod. A dose-dependent decrease in lymphocyte count was observed after initiation of cenerimod and reached a plateau (maximum change from baseline: −64%) after 20–23 days of treatment. Lymphocyte counts returned to baseline values at end-of-study examination. One serious adverse event of circulatory collapse (25 mg dose group, maximum tolerated dose: 10 mg) and adverse events of mild-to-moderate intensity were reported. Treatment initiation was associated with transient decreases in heart rate and blood pressure at doses >1 and ≥10 mg, respectively. View Full-Text
Keywords: pharmacokinetics; pharmacodynamics; S1P1 receptor modulator; lymphocyte; tolerability; food effect pharmacokinetics; pharmacodynamics; S1P1 receptor modulator; lymphocyte; tolerability; food effect
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Juif, P.-E.; Baldoni, D.; Reyes, M.; Wilbraham, D.; Febbraro, S.; Vaclavkova, A.; Hoch, M.; Dingemanse, J. Pharmacokinetics, Pharmacodynamics, Tolerability, and Food Effect of Cenerimod, a Selective S1P1 Receptor Modulator in Healthy Subjects. Int. J. Mol. Sci. 2017, 18, 2636.

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