Trial reportBritish journal of clinical pharmacology2013
Dose titration of BAF312 attenuates the initial heart rate reducing effect in healthy subjects.
Trial report in British journal of clinical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06639282 (SIPO1-AD), which is not on this map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
SIPO1-AD: A Phase II Clinical Trial for the Assessment of Safety, Tolerability, and Efficacy of Siponimod in Patients With Mild Alzheimer's Disease
Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Safety of S1P Modulators in Patients with Immune-Mediated Diseases: A Systematic Review and Meta-Analysis.Drug safety · 2021Pooled it
- First-in-human study of the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple oral doses of SAR247799, a selective G-protein-biased sphingosine-1 phosphate receptor-1 agonist for endothelial protection.British journal of clinical pharmacology · 2021Trial
- Population Pharmacokinetic Analysis of BMS-986166, a Novel Selective Sphingosine-1-Phosphate-1 Receptor Modulator, and Exposure-Response Assessment of Lymphocyte Counts and Heart Rate in Healthy Participants.Clinical pharmacology in drug development · 2021Trial
- Effect of Fluconazole Coadministration and CYP2C9 Genetic Polymorphism on Siponimod Pharmacokinetics in Healthy Subjects.Clinical pharmacokinetics · 2019Trial
- Cardiac Safety of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator: Results of a Thorough QT/QTc Study.Clinical pharmacology in drug development · 2018Trial
- Cardiac effects of amiselimod compared with fingolimod and placebo: results of a randomised, parallel-group, phase I study in healthy subjects.British journal of clinical pharmacology · 2017Trial
- PBPK Modeling and Clinical Data Reveal Reduced Impact of CYP3A4 and CYP2C9 Inhibitors on Elimination of Siponimod.Clinical and translational science · 2026Article
- Long-term effects of siponimod on cardiovascular and autonomic nervous system in secondary progressive multiple sclerosis.Frontiers in pharmacology · 2024Article
- Molecular and neuroimmune pharmacology of S1P receptor modulators and other disease-modifying therapies for multiple sclerosis.Pharmacology & therapeutics · 2023Review
- An update on the use of sphingosine 1-phosphate receptor modulators for the treatment of relapsing multiple sclerosis.Expert opinion on pharmacotherapy · 2023Review
- Pharmacokinetic Characteristics of Siponimod in Healthy Volunteers and Patients With Multiple Sclerosis: Analyses of Published Clinical Trials.Frontiers in pharmacology · 2022Article
- S1P receptor modulators and the cardiovascular autonomic nervous system in multiple sclerosis: a narrative review.Therapeutic advances in neurological disorders · 2022Review
- Review
- The role of sphingosine 1-phosphate and its receptors in cardiovascular diseases.Journal of cellular and molecular medicine · 2020Review
- Cardiodynamic Interactions between Two S1PInternational journal of molecular sciences · 2019Article
- First use of cenerimod, a selective S1PLupus science & medicine · 2019Article
- Siponimod pharmacokinetics, safety, and tolerability in combination with rifampin, a CYP2C9/3A4 inducer, in healthy subjects.European journal of clinical pharmacology · 2018Article
- Fingolimod-induced decrease in heart rate may predict subsequent decreasing degree of lymphocytes.Scientific reports · 2018Article
- Impact of siponimod on vaccination response in a randomized, placebo-controlled study.Neurology(R) neuroimmunology & neuroinflammation · 2017Article
- Sphingosine 1-Phosphate Receptor Modulators for the Treatment of Multiple Sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimPrevious studies have shown transient decreases in heart rate (HR) following administration of sphingosine 1-phosphate (S1P) receptor modulators including BAF312. This study was conducted to determine whether dose titration of BAF312 reduces or eliminates these effects.
methodsFifty-six healthy subjects were randomized 1:1:1:1 to receive BAF312 in one of two dose titration (DT) regimens (DT1 and DT2: 0.25-10 mg over 9-10 days), no titration (10 mg starting dose) or placebo. Pharmacodynamic and pharmacokinetic parameters were assessed.
resultsNeither DT1 nor DT2 resulted in clinically significant bradycardia or atrioventricular conduction effects. Both titration regimens showed a favourable difference on each of days 1-12 vs. the non-titration regimen on day 1 for HR effects (P < 0.0001). On day 1, the geometric mean ratio of the fraction from the previous day in minimum daily HR between DT1 and non-titration was 1.18 (95% confidence interval [CI] 1.13, 1.23) and 1.14 (95% CI 1.09, 1.18) for DT2 (both P < 0.05) with significant differences noted through to day 12. Non-titration HRs showed considerable separation from placebo throughout the study. There was no statistically significant reduction in HR vs. placebo on day 1 in either titration regimen. On days 3-7 subjects in DT1 and DT2 experienced minor reductions in HR vs. placebo (approximately 5 beats min⁻¹; P ≤ 0.0001). From days 9-12, HRs in both titration regimens were comparable with placebo.
conclusionBoth titration regimens effectively attenuated the initial bradyarrhythmia observed on day 1 of treatment with BAF312 10 mg.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.