Pharmacokinetics, Pharmacodynamics, Tolerability, and Food Effect of Cenerimod, a Selective S1P₁ Receptor Modulator in Healthy Subjects
| Autor: | Pierre-Eric, Juif, Daniela, Baldoni, Maribel, Reyes, Darren, Wilbraham, Salvatore, Febbraro, Andrea, Vaclavkova, Matthias, Hoch, Jasper, Dingemanse |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male Adolescent Dose-Response Relationship Drug Maximum Tolerated Dose Administration Oral Blood Pressure S1P1 receptor modulator Middle Aged lymphocyte Article Receptors Lysosphingolipid Renal Elimination Heart Rate pharmacodynamics food effect Humans Lymphocyte Count tolerability pharmacokinetics Immunosuppressive Agents |
| Zdroj: | International Journal of Molecular Sciences |
| ISSN: | 1422-0067 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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